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pmid:33693962

New insights for precision treatment of glioblastoma from analysis of single-cell lncRNA expression.

Qingkang Meng · Yan Zhang · Guoqi Li · Yunong Li · Hongbo Xie · Xiujie Chen

Journal of cancer research and clinical oncology · 2021 doi:10.1007/s00432-021-03584-9

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New insights for precision treatment of glioblastoma from analysis of single-cell lncRNA expression.
doi
10.1007/s00432-021-03584-9
pmid
33693962
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[0]
Qingkang Meng
[1]
Yan Zhang
[2]
Guoqi Li
[3]
Yunong Li
[4]
Hongbo Xie
[5]
Xiujie Chen
journal
Journal of cancer research and clinical oncology
year
2021
abstract
INTRODUCTION: Glioblastoma (GBM) is a complex disease with high intratumoral heterogeneity, understanding the molecular characteristics of intratumoral heterogeneity accurately is the basis for precision treatment. Although the existing typing strategy based on tumor molecular characteristics has a positive effect, there is still room for improvement, which is mainly because the traditional typing is completed based on the sequencing data of tissue samples, that is, the obtained data are the average level of patient tumor tissues, masking the intratumoral heterogeneity of a single patient and cannot reflect the real level of patient tumor cells. At present, cancer molecular typing is mostly performed based on transcriptome (RNA-seq) without considering lncRNA molecules that are also tissue-specific and developmental stage-specific. Therefore, in this study, we used lncRNAs as typing markers and combined single-cell expression profiles to retype glioblastoma, providing new ideas for GBM molecular typing, and further analyzed the shortcomings of traditional therapies at the singlecell level based on typing results and proposed new precise therapeutic insights. METHODS: We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing. The intratumoral heterogeneity of patients at the single-cell level was revealed using t-SNE, and the room for improvement of the existing traditional histotyping method was revealed using heat map and density curve. Subsequently, to validate the feasibility of lncRNA typing, we compared the similarities and differences of expression patterns between lncRNAs and mRNAs in GBM cells. Then, we used the R package "Seurat" to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs. For validation, we performed survival analysis on GBM tissue data from the TCGA database to reveal the impact of different subtypes on patient survival prognosis. Eventually, based on the results, we screened the therapeutic drugs of each subtype by targeting the downstream regulatory genes of lncRNAs and proposed a new precision therapeutic strategy. RESULTS: GBM has significant intratumoral heterogeneity at the single-cell level, with more than one traditional subtype highly expressed in each patient, which reflects the shortcomings of traditional histotyping. LncRNAs and mRNAs have similar expression patterns in GBM cells, and the expression coefficient of variation of lncRNAs is higher than that of mRNAs, meaning that lncRNAs will better reflect the intratumoral heterogeneity. GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics. Survival analysis showed that patients with different subtype compositions had different prognostic outcomes, so different subtypes had different effects on patient prognosis. Based on this, 47 drugs were screened for treatment. There are both shared and unique drugs between different subtypes. A new precision treatment strategy was proposed: for patients with different subtypes, in addition to the combination of drugs targeting single subtype, drugs targeting multiple subtypes can also be selected. CONCLUSION: Intratumoral heterogeneity may lead to poor prognosis or recurrence after treatment, and more precise typing of GBM can be performed based on single-cell lncRNA expression profiles. The biological characteristics possessed by different subtypes will have different effects on patients, such as survival time. For different subtypes, there are both drugs targeting single subtype and drugs targeting multiple subtypes, and we prefer drugs targeting multiple subtypes because this strategy can maximize medication efficiency and reduce the types of medication to reduce risks and side effects.
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Then, we used the R package “Seurat” to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs.
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Then, we used the R package “Seurat” to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs.
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We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing.
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GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics.
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GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics.
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GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics.
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[452]
GSM2243897
[453]
GSM2243898
[454]
GSM2243899
[455]
GSM2243900
[456]
GSM2243901
[457]
GSM2243902
[458]
GSM2243903
[459]
GSM2243904
[460]
GSM2243905
[461]
GSM2243906
[462]
GSM2243907
[463]
GSM2243908
[464]
GSM2243909
[465]
GSM2243910
[466]
GSM2243911
[467]
GSM2243912
[468]
GSM2243913
[469]
GSM2243914
[470]
GSM2243915
[471]
GSM2243916
[472]
GSM2243917
[473]
GSM2243918
[474]
GSM2243919
[475]
GSM2243920
[476]
GSM2243921
[477]
GSM2243922
[478]
GSM2243923
[479]
GSM2243924
[480]
GSM2243925
[481]
GSM2243926
[482]
GSM2243927
[483]
GSM2243928
[484]
GSM2243929
[485]
GSM2243930
[486]
GSM2243931
[487]
GSM2243932
[488]
GSM2243933
[489]
GSM2243934
[490]
GSM2243935
[491]
GSM2243936
[492]
GSM2243937
[493]
GSM2243938
[494]
GSM2243939
[495]
GSM2243940
[496]
GSM2243941
[497]
GSM2243942
[498]
GSM2243943
[499]
GSM2243944
[500]
GSM2243945
[501]
GSM2243946
[502]
GSM2243947
[503]
GSM2243948
[504]
GSM2243949
[505]
GSM2243950
[506]
GSM2243951
[507]
GSM2243952
[508]
GSM2243953
[509]
GSM2243954
[510]
GSM2243955
[511]
GSM2243956
[512]
GSM2243957
[513]
GSM2243958
[514]
GSM2243959
[515]
GSM2243960
[516]
GSM2243961
[517]
GSM2243962
[518]
GSM2243963
[519]
GSM2243964
[520]
GSM2243965
[521]
GSM2243966
[522]
GSM2243967
[523]
GSM2243968
[524]
GSM2243969
[525]
GSM2243970
[526]
GSM2243971
[527]
GSM2243972
[528]
GSM2243973
[529]
GSM2243974
[530]
GSM2243975
[531]
GSM2243976
[532]
GSM2243977
[533]
GSM2243978
[534]
GSM2243979
[535]
GSM2243980
[536]
GSM2243981
[537]
GSM2243982
[538]
GSM2243983
[539]
GSM2243984
[540]
GSM2243985
[541]
GSM2243986
[542]
GSM2243987
[543]
GSM2243988
[544]
GSM2243989
[545]
GSM2243990
[546]
GSM2243991
[547]
GSM2243992
[548]
GSM2243993
[549]
GSM2243994
[550]
GSM2243995
[551]
GSM2243996
[552]
GSM2243997
[553]
GSM2243998
[554]
GSM2243999
[555]
GSM2244000
[556]
GSM2244001
[557]
GSM2244002
[558]
GSM2244003
[559]
GSM2244004
[560]
GSM2244005
[561]
GSM2244006
[562]
GSM2244007
[563]
GSM2244008
[564]
GSM2244009
[565]
GSM2244010
[566]
GSM2244011
[567]
GSM2244012
[568]
GSM2244013
[569]
GSM2244014
[570]
GSM2244015
[571]
GSM2244016
[572]
GSM2244017
[573]
GSM2244018
[574]
GSM2244019
[575]
GSM2244020
[576]
GSM2244021
[577]
GSM2244022
[578]
GSM2244023
[579]
GSM2244024
[580]
GSM2244025
[581]
GSM2244026
[582]
GSM2244027
[583]
GSM2244028
[584]
GSM2244029
[585]
GSM2244030
[586]
GSM2244031
[587]
GSM2244032
[588]
GSM2244033
[589]
GSM2244034
[590]
GSM2244035
[591]
GSM2244036
[592]
GSM2244037
[593]
GSM2244038
[594]
GSM2244039
[595]
GSM2244040
[596]
GSM2244041
[597]
GSM2244042
[598]
GSM2244043
[599]
GSM2244044
[600]
GSM2244045
[601]
GSM2244046
[602]
GSM2244047
[603]
GSM2244048
[604]
GSM2244049
[605]
GSM2244050
[606]
GSM2244051
[607]
GSM2244052
[608]
GSM2244053
[609]
GSM2244054
[610]
GSM2244055
[611]
GSM2244056
[612]
GSM2244057
[613]
GSM2244058
[614]
GSM2244059
[615]
GSM2244060
[616]
GSM2244061
[617]
GSM2244062
[618]
GSM2244063
[619]
GSM2244064
[620]
GSM2244065
[621]
GSM2244066
[622]
GSM2244067
[623]
GSM2244068
[624]
GSM2244069
[625]
GSM2244070
[626]
GSM2244071
[627]
GSM2244072
[628]
GSM2244073
[629]
GSM2244074
[630]
GSM2244075
[631]
GSM2244076
[632]
GSM2244077
[633]
GSM2244078
[634]
GSM2244079
[635]
GSM2244080
[636]
GSM2244081
[637]
GSM2244082
[638]
GSM2244083
[639]
GSM2244084
[640]
GSM2244085
[641]
GSM2244086
[642]
GSM2244087
[643]
GSM2244088
[644]
GSM2244089
[645]
GSM2244090
[646]
GSM2244091
[647]
GSM2244092
[648]
GSM2244093
[649]
GSM2244094
[650]
GSM2244095
[651]
GSM2244096
[652]
GSM2244097
[653]
GSM2244098
[654]
GSM2244099
[655]
GSM2244100
[656]
GSM2244101
[657]
GSM2244102
[658]
GSM2244103
[659]
GSM2244104
[660]
GSM2244105
[661]
GSM2244106
[662]
GSM2244107
[663]
GSM2244108
[664]
GSM2244109
[665]
GSM2244110
[666]
GSM2244111
[667]
GSM2244112
[668]
GSM2244113
[669]
GSM2244114
[670]
GSM2244115
[671]
GSM2244116
[672]
GSM2244117
[673]
GSM2244118
[674]
GSM2244119
[675]
GSM2244120
[676]
GSM2244121
[677]
GSM2244122
[678]
GSM2244123
[679]
GSM2244124
[680]
GSM2244125
[681]
GSM2244126
[682]
GSM2244127
[683]
GSM2244128
[684]
GSM2244129
[685]
GSM2244130
[686]
GSM2244131
[687]
GSM2244132
[688]
GSM2244133
[689]
GSM2244134
[690]
GSM2244135
[691]
GSM2244136
[692]
GSM2244137
[693]
GSM2244138
[694]
GSM2244139
[695]
GSM2244140
[696]
GSM2244141
[697]
GSM2244142
[698]
GSM2244143
[699]
GSM2244144
[700]
GSM2244145
[701]
GSM2244146
[702]
GSM2244147
[703]
GSM2244148
[704]
GSM2244149
[705]
GSM2244150
[706]
GSM2244151
[707]
GSM2244152
[708]
GSM2244153
[709]
GSM2244154
[710]
GSM2244155
[711]
GSM2244156
[712]
GSM2244157
[713]
GSM2244158
[714]
GSM2244159
[715]
GSM2244160
[716]
GSM2244161
[717]
GSM2244162
[718]
GSM2244163
[719]
GSM2244164
[720]
GSM2244165
[721]
GSM2244166
[722]
GSM2244167
[723]
GSM2244168
[724]
GSM2244169
[725]
GSM2244170
[726]
GSM2244171
[727]
GSM2244172
[728]
GSM2244173
[729]
GSM2244174
[730]
GSM2244175
[731]
GSM2244176
[732]
GSM2244177
[733]
GSM2244178
[734]
GSM2244179
[735]
GSM2244180
[736]
GSM2244181
[737]
GSM2244182
[738]
GSM2244183
[739]
GSM2244184
[740]
GSM2244185
[741]
GSM2244186
[742]
GSM2244187
[743]
GSM2244188
[744]
GSM2244189
[745]
GSM2244190
[746]
GSM2244191
[747]
GSM2244192
[748]
GSM2244193
[749]
GSM2244194
[750]
GSM2244195
[751]
GSM2244196
[752]
GSM2244197
[753]
GSM2244198
[754]
GSM2244199
[755]
GSM2244200
[756]
GSM2244201
[757]
GSM2244202
[758]
GSM2244203
[759]
GSM2244204
[760]
GSM2244205
[761]
GSM2244206
[762]
GSM2244207
[763]
GSM2244208
[764]
GSM2244209
[765]
GSM2244210
[766]
GSM2244211
[767]
GSM2244212
[768]
GSM2244213
[769]
GSM2244214
[770]
GSM2244215
[771]
GSM2244216
[772]
GSM2244217
[773]
GSM2244218
[774]
GSM2244219
[775]
GSM2244220
[776]
GSM2244221
[777]
GSM2244222
[778]
GSM2244223
[779]
GSM2244224
[780]
GSM2244225
[781]
GSM2244226
[782]
GSM2244227
[783]
GSM2244228
[784]
GSM2244229
[785]
GSM2244230
[786]
GSM2244231
[787]
GSM2244232
[788]
GSM2244233
[789]
GSM2244234
[790]
GSM2244235
[791]
GSM2244236
[792]
GSM2244237
[793]
GSM2244238
[794]
GSM2244239
[795]
GSM2244240
[796]
GSM2244241
[797]
GSM2244242
[798]
GSM2244243
[799]
GSM2244244
[800]
GSM2244245
[801]
GSM2244246
[802]
GSM2244247
[803]
GSM2244248
[804]
GSM2244249
[805]
GSM2244250
[806]
GSM2244251
[807]
GSM2244252
[808]
GSM2244253
[809]
GSM2244254
[810]
GSM2244255
[811]
GSM2244256
[812]
GSM2244257
[813]
GSM2244258
[814]
GSM2244259
[815]
GSM2244260
[816]
GSM2244261
[817]
GSM2244262
[818]
GSM2244263
[819]
GSM2244264
[820]
GSM2244265
[821]
GSM2244266
[822]
GSM2244267
[823]
GSM2244268
[824]
GSM2244269
[825]
GSM2244270
[826]
GSM2244271
[827]
GSM2244272
[828]
GSM2244273
[829]
GSM2244274
[830]
GSM2244275
[831]
GSM2244276
[832]
GSM2244277
[833]
GSM2244278
[834]
GSM2244279
[835]
GSM2244280
[836]
GSM2244281
[837]
GSM2244282
[838]
GSM2244283
[839]
GSM2244284
[840]
GSM2244285
[841]
GSM2244286
[842]
GSM2244287
[843]
GSM2244288
[844]
GSM2244289
[845]
GSM2244290
[846]
GSM2244291
[847]
GSM2244292
[848]
GSM2244293
[849]
GSM2244294
[850]
GSM2244295
[851]
GSM2244296
[852]
GSM2244297
[853]
GSM2244298
[854]
GSM2244299
[855]
GSM2244300
[856]
GSM2244301
[857]
GSM2244302
[858]
GSM2244303
[859]
GSM2244304
[860]
GSM2244305
[861]
GSM2244306
[862]
GSM2244307
[863]
GSM2244308
[864]
GSM2244309
[865]
GSM2244310
[866]
GSM2244311
[867]
GSM2244312
[868]
GSM2244313
[869]
GSM2244314
[870]
GSM2244315
[871]
GSM2244316
[872]
GSM2244317
[873]
GSM2244318
[874]
GSM2244319
[875]
GSM2244320
[876]
GSM2244321
[877]
GSM2244322
[878]
GSM2244323
[879]
GSM2244324
[880]
GSM2244325
[881]
GSM2244326
[882]
GSM2244327
[883]
GSM2244328
[884]
GSM2244329
[885]
GSM2244330
[886]
GSM2244331
[887]
GSM2244332
[888]
GSM2244333
[889]
GSM2244334
[890]
GSM2244335
[891]
GSM2244336
[892]
GSM2244337
[893]
GSM2244338
[894]
GSM2244339
[895]
GSM2244340
[896]
GSM2244341
[897]
GSM2244342
[898]
GSM2244343
[899]
GSM2244344
[900]
GSM2244345
[901]
GSM2244346
[902]
GSM2244347
[903]
GSM2244348
[904]
GSM2244349
[905]
GSM2244350
[906]
GSM2244351
[907]
GSM2244352
[908]
GSM2244353
[909]
GSM2244354
[910]
GSM2244355
[911]
GSM2244356
[912]
GSM2244357
[913]
GSM2244358
[914]
GSM2244359
[915]
GSM2244360
[916]
GSM2244361
[917]
GSM2244362
[918]
GSM2244363
[919]
GSM2244364
[920]
GSM2244365
[921]
GSM2244366
[922]
GSM2244367
[923]
GSM2244368
[924]
GSM2244369
[925]
GSM2244370
[926]
GSM2244371
[927]
GSM2244372
[928]
GSM2244373
[929]
GSM2244374
[930]
GSM2244375
[931]
GSM2244376
[932]
GSM2244377
[933]
GSM2244378
[934]
GSM2244379
[935]
GSM2244380
[936]
GSM2244381
[937]
GSM2244382
[938]
GSM2244383
[939]
GSM2244384
[940]
GSM2244385
[941]
GSM2244386
[942]
GSM2244387
[943]
GSM2244388
[944]
GSM2244389
[945]
GSM2244390
[946]
GSM2244391
[947]
GSM2244392
[948]
GSM2244393
[949]
GSM2244394
[950]
GSM2244395
[951]
GSM2244396
[952]
GSM2244397
[953]
GSM2244398
[954]
GSM2244399
[955]
GSM2244400
[956]
GSM2244401
[957]
GSM2244402
[958]
GSM2244403
[959]
GSM2244404
[960]
GSM2244405
[961]
GSM2244406
[962]
GSM2244407
[963]
GSM2244408
[964]
GSM2244409
[965]
GSM2244410
[966]
GSM2244411
[967]
GSM2244412
[968]
GSM2244413
[969]
GSM2244414
[970]
GSM2244415
[971]
GSM2244416
[972]
GSM2244417
[973]
GSM2244418
[974]
GSM2244419
[975]
GSM2244420
[976]
GSM2244421
[977]
GSM2244422
[978]
GSM2244423
[979]
GSM2244424
[980]
GSM2244425
[981]
GSM2244426
[982]
GSM2244427
[983]
GSM2244428
[984]
GSM2244429
[985]
GSM2244430
[986]
GSM2244431
[987]
GSM2244432
[988]
GSM2244433
[989]
GSM2244434
[990]
GSM2244435
[991]
GSM2244436
[992]
GSM2244437
[993]
GSM2244438
[994]
GSM2244439
[995]
GSM2244440
[996]
GSM2244441
[997]
GSM2244442
[998]
GSM2244443
[999]
GSM2244444
[1000]
GSM2244445
[1001]
GSM2244446
[1002]
GSM2244447
[1003]
GSM2244448
[1004]
GSM2244449
[1005]
GSM2244450
[1006]
GSM2244451
[1007]
GSM2244452
[1008]
GSM2244453
[1009]
GSM2244454
[1010]
GSM2244455
[1011]
GSM2244456
[1012]
GSM2244457
[1013]
GSM2244458
[1014]
GSM2244459
[1015]
GSM2244460
[1016]
GSM2244461
[1017]
GSM2244462
[1018]
GSM2244463
[1019]
GSM2244464
[1020]
GSM2244465
[1021]
GSM2244466
[1022]
GSM2244467
[1023]
GSM2244468
[1024]
GSM2244469
[1025]
GSM2244470
[1026]
GSM2244471
[1027]
GSM2244472
[1028]
GSM2244473
[1029]
GSM2244474
[1030]
GSM2244475
[1031]
GSM2244476
[1032]
GSM2244477
[1033]
GSM2244478
[1034]
GSM2244479
[1035]
GSM2244480
[1036]
GSM2244481
[1037]
GSM2244482
[1038]
GSM2244483
[1039]
GSM2244484
[1040]
GSM2244485
[1041]
GSM2244486
[1042]
GSM2244487
[1043]
GSM2244488
[1044]
GSM2244489
[1045]
GSM2244490
[1046]
GSM2244491
[1047]
GSM2244492
[1048]
GSM2244493
[1049]
GSM2244494
[1050]
GSM2244495
[1051]
GSM2244496
[1052]
GSM2244497
[1053]
GSM2244498
[1054]
GSM2244499
[1055]
GSM2244500
[1056]
GSM2244501
[1057]
GSM2244502
[1058]
GSM2244503
[1059]
GSM2244504
[1060]
GSM2244505
[1061]
GSM2244506
[1062]
GSM2244507
[1063]
GSM2244508
[1064]
GSM2244509
[1065]
GSM2244510
[1066]
GSM2244511
[1067]
GSM2244512
[1068]
GSM2244513
[1069]
GSM2244514
[1070]
GSM2244515
[1071]
GSM2244516
[1072]
GSM2244517
[1073]
GSM2244518
[1074]
GSM2244519
[1075]
GSM2244520
[1076]
GSM2244521
[1077]
GSM2244522
[1078]
GSM2244523
[1079]
GSM2244524
[1080]
GSM2244525
[1081]
GSM2244526
[1082]
GSM2244527
[1083]
GSM2244528
[1084]
GSM2244529
[1085]
GSM2244530
[1086]
GSM2244531
[1087]
GSM2244532
[1088]
GSM2244533
[1089]
GSM2244534
[1090]
GSM2244535
[1091]
GSM2244536
[1092]
GSM2244537
[1093]
GSM2244538
[1094]
GSM2244539
[1095]
GSM2244540
[1096]
GSM2244541
[1097]
GSM2244542
[1098]
GSM2244543
[1099]
GSM2244544
[1100]
GSM2244545
[1101]
GSM2244546
[1102]
GSM2244547
[1103]
GSM2244548
[1104]
GSM2244549
[1105]
GSM2244550
[1106]
GSM2244551
[1107]
GSM2244552
[1108]
GSM2244553
[1109]
GSM2244554
[1110]
GSM2244555
[1111]
GSM2244556
[1112]
GSM2244557
[1113]
GSM2244558
[1114]
GSM2244559
[1115]
GSM2244560
[1116]
GSM2244561
[1117]
GSM2244562
[1118]
GSM2244563
[1119]
GSM2244564
[1120]
GSM2244565
[1121]
GSM2244566
[1122]
GSM2244567
[1123]
GSM2244568
[1124]
GSM2244569
[1125]
GSM2244570
[1126]
GSM2244571
[1127]
GSM2244572
[1128]
GSM2244573
[1129]
GSM2244574
[1130]
GSM2244575
[1131]
GSM2244576
[1132]
GSM2244577
[1133]
GSM2244578
[1134]
GSM2244579
[1135]
GSM2244580
[1136]
GSM2244581
[1137]
GSM2244582
[1138]
GSM2244583
[1139]
GSM2244584
[1140]
GSM2244585
[1141]
GSM2244586
[1142]
GSM2244587
[1143]
GSM2244588
[1144]
GSM2244589
[1145]
GSM2244590
[1146]
GSM2244591
[1147]
GSM2244592
[1148]
GSM2244593
[1149]
GSM2244594
[1150]
GSM2244595
[1151]
GSM2244596
[1152]
GSM2244597
[1153]
GSM2244598
[1154]
GSM2244599
[1155]
GSM2244600
[1156]
GSM2244601
[1157]
GSM2244602
[1158]
GSM2244603
[1159]
GSM2244604
[1160]
GSM2244605
[1161]
GSM2244606
[1162]
GSM2244607
[1163]
GSM2244608
[1164]
GSM2244609
[1165]
GSM2244610
[1166]
GSM2244611
[1167]
GSM2244612
[1168]
GSM2244613
[1169]
GSM2244614
[1170]
GSM2244615
[1171]
GSM2244616
[1172]
GSM2244617
[1173]
GSM2244618
[1174]
GSM2244619
[1175]
GSM2244620
[1176]
GSM2244621
[1177]
GSM2244622
[1178]
GSM2244623
[1179]
GSM2244624
[1180]
GSM2244625
[1181]
GSM2244626
[1182]
GSM2244627
[1183]
GSM2244628
[1184]
GSM2244629
[1185]
GSM2244630
[1186]
GSM2244631
[1187]
GSM2244632
[1188]
GSM2244633
[1189]
GSM2244634
[1190]
GSM2244635
[1191]
GSM2244636
[1192]
GSM2244637
[1193]
GSM2244638
[1194]
GSM2244639
[1195]
GSM2244640
[1196]
GSM2244641
[1197]
GSM2244642
[1198]
GSM2244643
[1199]
GSM2244644
[1200]
GSM2244645
[1201]
GSM2244646
[1202]
GSM2244647
[1203]
GSM2244648
[1204]
GSM2244649
[1205]
GSM2244650
[1206]
GSM2244651
[1207]
GSM2244652
[1208]
GSM2244653
[1209]
GSM2244654
[1210]
GSM2244655
[1211]
GSM2244656
[1212]
GSM2244657
[1213]
GSM2244658
[1214]
GSM2244659
[1215]
GSM2244660
[1216]
GSM2244661
[1217]
GSM2244662
[1218]
GSM2244663
[1219]
GSM2244664
[1220]
GSM2244665
[1221]
GSM2244666
[1222]
GSM2244667
[1223]
GSM2244668
[1224]
GSM2244669
[1225]
GSM2244670
[1226]
GSM2244671
[1227]
GSM2244672
[1228]
GSM2244673
[1229]
GSM2244674
[1230]
GSM2244675
[1231]
GSM2244676
[1232]
GSM2244677
[1233]
GSM2244678
[1234]
GSM2244679
[1235]
GSM2244680
[1236]
GSM2244681
[1237]
GSM2244682
[1238]
GSM2244683
[1239]
GSM2244684
[1240]
GSM2244685
[1241]
GSM2244686
[1242]
GSM2244687
[1243]
GSM2244688
[1244]
GSM2244689
[1245]
GSM2244690
[1246]
GSM2244691
[1247]
GSM2244692
[1248]
GSM2244693
[1249]
GSM2244694
[1250]
GSM2244695
[1251]
GSM2244696
[1252]
GSM2244697
[1253]
GSM2244698
[1254]
GSM2244699
[1255]
GSM2244700
[1256]
GSM2244701
[1257]
GSM2244702
[1258]
GSM2244703
[1259]
GSM2244704
[1260]
GSM2244705
[1261]
GSM2244706
[1262]
GSM2244707
[1263]
GSM2244708
[1264]
GSM2244709
[1265]
GSM2244710
[1266]
GSM2244711
[1267]
GSM2244712
[1268]
GSM2244713
[1269]
GSM2244714
[1270]
GSM2244715
[1271]
GSM2244716
[1272]
GSM2244717
[1273]
GSM2244718
[1274]
GSM2244719
[1275]
GSM2244720
[1276]
GSM2244721
[1277]
GSM2244722
[1278]
GSM2244723
[1279]
GSM2244724
[1280]
GSM2244725
[1281]
GSM2244726
[1282]
GSM2244727
[1283]
GSM2244728
[1284]
GSM2244729
[1285]
GSM2244730
[1286]
GSM2244731
[1287]
GSM2244732
[1288]
GSM2244733
[1289]
GSM2244734
[1290]
GSM2244735
[1291]
GSM2244736
[1292]
GSM2244737
[1293]
GSM2244738
[1294]
GSM2244739
[1295]
GSM2244740
[1296]
GSM2244741
[1297]
GSM2244742
[1298]
GSM2244743
[1299]
GSM2244744
[1300]
GSM2244745
[1301]
GSM2244746
[1302]
GSM2244747
[1303]
GSM2244748
[1304]
GSM2244749
[1305]
GSM2244750
[1306]
GSM2244751
[1307]
GSM2244752
[1308]
GSM2244753
[1309]
GSM2244754
[1310]
GSM2244755
[1311]
GSM2244756
[1312]
GSM2244757
[1313]
GSM2244758
[1314]
GSM2244759
[1315]
GSM2244760
[1316]
GSM2244761
[1317]
GSM2244762
[1318]
GSM2244763
[1319]
GSM2244764
[1320]
GSM2244765
[1321]
GSM2244766
[1322]
GSM2244767
[1323]
GSM2244768
[1324]
GSM2244769
[1325]
GSM2244770
[1326]
GSM2244771
[1327]
GSM2244772
[1328]
GSM2244773
[1329]
GSM2244774
[1330]
GSM2244775
[1331]
GSM2244776
[1332]
GSM2244777
[1333]
GSM2244778
[1334]
GSM2244779
[1335]
GSM2244780
[1336]
GSM2244781
[1337]
GSM2244782
[1338]
GSM2244783
[1339]
GSM2244784
[1340]
GSM2244785
[1341]
GSM2244786
[1342]
GSM2244787
[1343]
GSM2244788
[1344]
GSM2244789
[1345]
GSM2244790
[1346]
GSM2244791
[1347]
GSM2244792
[1348]
GSM2244793
[1349]
GSM2244794
[1350]
GSM2244795
[1351]
GSM2244796
[1352]
GSM2244797
[1353]
GSM2244798
[1354]
GSM2244799
[1355]
GSM2244800
[1356]
GSM2244801
[1357]
GSM2244802
[1358]
GSM2244803
[1359]
GSM2244804
[1360]
GSM2244805
[1361]
GSM2244806
[1362]
GSM2244807
[1363]
GSM2244808
[1364]
GSM2244809
[1365]
GSM2244810
[1366]
GSM2244811
[1367]
GSM2244812
[1368]
GSM2244813
[1369]
GSM2244814
[1370]
GSM2244815
[1371]
GSM2244816
[1372]
GSM2244817
[1373]
GSM2244818
[1374]
GSM2244819
[1375]
GSM2244820
[1376]
GSM2244821
[1377]
GSM2244822
[1378]
GSM2244823
[1379]
GSM2244824
[1380]
GSM2244825
[1381]
GSM2244826
[1382]
GSM2244827
[1383]
GSM2244828
[1384]
GSM2244829
[1385]
GSM2244830
[1386]
GSM2244831
[1387]
GSM2244832
[1388]
GSM2244833
[1389]
GSM2244834
[1390]
GSM2244835
[1391]
GSM2244836
[1392]
GSM2244837
[1393]
GSM2244838
[1394]
GSM2244839
[1395]
GSM2244840
[1396]
GSM2244841
[1397]
GSM2244842
[1398]
GSM2244843
[1399]
GSM2244844
[1400]
GSM2244845
[1401]
GSM2244846
[1402]
GSM2244847
[1403]
GSM2244848
[1404]
GSM2244849
[1405]
GSM2244850
[1406]
GSM2244851
[1407]
GSM2244852
[1408]
GSM2244853
[1409]
GSM2244854
[1410]
GSM2244855
[1411]
GSM2244856
[1412]
GSM2244857
[1413]
GSM2244858
[1414]
GSM2244859
[1415]
GSM2244860
[1416]
GSM2244861
[1417]
GSM2244862
[1418]
GSM2244863
[1419]
GSM2244864
[1420]
GSM2244865
[1421]
GSM2244866
[1422]
GSM2244867
[1423]
GSM2244868
[1424]
GSM2244869
[1425]
GSM2244870
[1426]
GSM2244871
[1427]
GSM2244872
[1428]
GSM2244873
[1429]
GSM2244874
[1430]
GSM2244875
[1431]
GSM2244876
[1432]
GSM2244877
[1433]
GSM2244878
[1434]
GSM2244879
[1435]
GSM2244880
[1436]
GSM2244881
[1437]
GSM2244882
[1438]
GSM2244883
[1439]
GSM2244884
[1440]
GSM2244885
[1441]
GSM2244886
[1442]
GSM2244887
[1443]
GSM2244888
[1444]
GSM2244889
[1445]
GSM2244890
[1446]
GSM2244891
[1447]
GSM2244892
[1448]
GSM2244893
[1449]
GSM2244894
[1450]
GSM2244895
[1451]
GSM2244896
[1452]
GSM2244897
[1453]
GSM2244898
[1454]
GSM2244899
[1455]
GSM2244900
[1456]
GSM2244901
[1457]
GSM2244902
[1458]
GSM2244903
[1459]
GSM2244904
[1460]
GSM2244905
[1461]
GSM2244906
[1462]
GSM2244907
[1463]
GSM2244908
[1464]
GSM2244909
[1465]
GSM2244910
[1466]
GSM2244911
[1467]
GSM2244912
[1468]
GSM2244913
[1469]
GSM2244914
[1470]
GSM2244915
[1471]
GSM2244916
[1472]
GSM2244917
[1473]
GSM2244918
[1474]
GSM2244919
[1475]
GSM2244920
[1476]
GSM2244921
[1477]
GSM2244922
[1478]
GSM2244923
[1479]
GSM2244924
[1480]
GSM2244925
[1481]
GSM2244926
[1482]
GSM2244927
[1483]
GSM2244928
[1484]
GSM2244929
[1485]
GSM2244930
[1486]
GSM2244931
[1487]
GSM2244932
[1488]
GSM2244933
[1489]
GSM2244934
[1490]
GSM2244935
[1491]
GSM2244936
[1492]
GSM2244937
[1493]
GSM2244938
[1494]
GSM2244939
[1495]
GSM2244940
[1496]
GSM2244941
[1497]
GSM2244942
[1498]
GSM2244943
[1499]
GSM2244944
[1500]
GSM2244945
[1501]
GSM2244946
[1502]
GSM2244947
[1503]
GSM2244948
[1504]
GSM2244949
[1505]
GSM2244950
[1506]
GSM2244951
[1507]
GSM2244952
[1508]
GSM2244953
[1509]
GSM2244954
[1510]
GSM2244955
[1511]
GSM2244956
[1512]
GSM2244957
[1513]
GSM2244958
[1514]
GSM2244959
[1515]
GSM2244960
[1516]
GSM2244961
[1517]
GSM2244962
[1518]
GSM2244963
[1519]
GSM2244964
[1520]
GSM2244965
[1521]
GSM2244966
[1522]
GSM2244967
[1523]
GSM2244968
[1524]
GSM2244969
[1525]
GSM2244970
[1526]
GSM2244971
[1527]
GSM2244972
[1528]
GSM2244973
[1529]
GSM2244974
[1530]
GSM2244975
[1531]
GSM2244976
[1532]
GSM2244977
[1533]
GSM2244978
[1534]
GSM2244979
[1535]
GSM2244980
[1536]
GSM2244981
[1537]
GSM2244982
[1538]
GSM2244983
[1539]
GSM2244984
[1540]
GSM2244985
[1541]
GSM2244986
[1542]
GSM2244987
[1543]
GSM2244988
[1544]
GSM2244989
[1545]
GSM2244990
[1546]
GSM2244991
[1547]
GSM2244992
[1548]
GSM2244993
[1549]
GSM2244994
[1550]
GSM2244995
[1551]
GSM2244996
[1552]
GSM2244997
[1553]
GSM2244998
[1554]
GSM2244999
[1555]
GSM2245000
[1556]
GSM2245001
[1557]
GSM2245002
[1558]
GSM2245003
[1559]
GSM2245004
[1560]
GSM2245005
[1561]
GSM2245006
[1562]
GSM2245007
[1563]
GSM2245008
[1564]
GSM2245009
[1565]
GSM2245010
[1566]
GSM2245011
[1567]
GSM2245012
[1568]
GSM2245013
[1569]
GSM2245014
[1570]
GSM2245015
[1571]
GSM2245016
[1572]
GSM2245017
[1573]
GSM2245018
[1574]
GSM2245019
[1575]
GSM2245020
[1576]
GSM2245021
[1577]
GSM2245022
[1578]
GSM2245023
[1579]
GSM2245024
[1580]
GSM2245025
[1581]
GSM2245026
[1582]
GSM2245027
[1583]
GSM2245028
[1584]
GSM2245029
[1585]
GSM2245030
[1586]
GSM2245031
[1587]
GSM2245032
[1588]
GSM2245033
[1589]
GSM2245034
[1590]
GSM2245035
[1591]
GSM2245036
[1592]
GSM2245037
[1593]
GSM2245038
[1594]
GSM2245039
[1595]
GSM2245040
[1596]
GSM2245041
[1597]
GSM2245042
[1598]
GSM2245043
[1599]
GSM2245044
[1600]
GSM2245045
[1601]
GSM2245046
[1602]
GSM2245047
[1603]
GSM2245048
[1604]
GSM2245049
[1605]
GSM2245050
[1606]
GSM2245051
[1607]
GSM2245052
[1608]
GSM2245053
[1609]
GSM2245054
[1610]
GSM2245055
[1611]
GSM2245056
[1612]
GSM2245057
[1613]
GSM2245058
[1614]
GSM2245059
[1615]
GSM2245060
[1616]
GSM2245061
[1617]
GSM2245062
[1618]
GSM2245063
[1619]
GSM2245064
[1620]
GSM2245065
[1621]
GSM2245066
[1622]
GSM2245067
[1623]
GSM2245068
[1624]
GSM2245069
[1625]
GSM2245070
[1626]
GSM2245071
[1627]
GSM2245072
[1628]
GSM2245073
[1629]
GSM2245074
[1630]
GSM2245075
[1631]
GSM2245076
[1632]
GSM2245077
[1633]
GSM2245078
[1634]
GSM2245079
[1635]
GSM2245080
[1636]
GSM2245081
[1637]
GSM2245082
[1638]
GSM2245083
[1639]
GSM2245084
[1640]
GSM2245085
[1641]
GSM2245086
[1642]
GSM2245087
[1643]
GSM2245088
[1644]
GSM2245089
[1645]
GSM2245090
[1646]
GSM2245091
[1647]
GSM2245092
[1648]
GSM2245093
[1649]
GSM2245094
[1650]
GSM2245095
[1651]
GSM2245096
[1652]
GSM2245097
[1653]
GSM2245098
[1654]
GSM2245099
[1655]
GSM2245100
[1656]
GSM2245101
[1657]
GSM2245102
[1658]
GSM2245103
[1659]
GSM2245104
[1660]
GSM2245105
[1661]
GSM2245106
[1662]
GSM2245107
[1663]
GSM2245108
[1664]
GSM2245109
[1665]
GSM2245110
[1666]
GSM2245111
[1667]
GSM2245112
[1668]
GSM2245113
[1669]
GSM2245114
[1670]
GSM2245115
[1671]
GSM2245116
[1672]
GSM2245117
[1673]
GSM2245118
[1674]
GSM2245119
[1675]
GSM2245120
[1676]
GSM2245121
[1677]
GSM2245122
[1678]
GSM2245123
[1679]
GSM2245124
[1680]
GSM2245125
[1681]
GSM2245126
[1682]
GSM2245127
[1683]
GSM2245128
[1684]
GSM2245129
[1685]
GSM2245130
[1686]
GSM2245131
[1687]
GSM2245132
[1688]
GSM2245133
[1689]
GSM2245134
[1690]
GSM2245135
[1691]
GSM2245136
[1692]
GSM2245137
[1693]
GSM2245138
[1694]
GSM2245139
[1695]
GSM2245140
[1696]
GSM2245141
[1697]
GSM2245142
[1698]
GSM2245143
[1699]
GSM2245144
[1700]
GSM2245145
[1701]
GSM2245146
[1702]
GSM2245147
[1703]
GSM2245148
[1704]
GSM2245149
[1705]
GSM2245150
[1706]
GSM2245151
[1707]
GSM2245152
[1708]
GSM2245153
[1709]
GSM2245154
[1710]
GSM2245155
[1711]
GSM2245156
[1712]
GSM2245157
[1713]
GSM2245158
[1714]
GSM2245159
[1715]
GSM2245160
[1716]
GSM2245161
[1717]
GSM2245162
[1718]
GSM2245163
[1719]
GSM2245164
[1720]
GSM2245165
[1721]
GSM2245166
[1722]
GSM2245167
[1723]
GSM2245168
[1724]
GSM2245169
[1725]
GSM2245170
[1726]
GSM2245171
[1727]
GSM2245172
[1728]
GSM2245173
[1729]
GSM2245174
[1730]
GSM2245175
[1731]
GSM2245176
[1732]
GSM2245177
[1733]
GSM2245178
[1734]
GSM2245179
[1735]
GSM2245180
[1736]
GSM2245181
[1737]
GSM2245182
[1738]
GSM2245183
[1739]
GSM2245184
[1740]
GSM2245185
[1741]
GSM2245186
[1742]
GSM2245187
[1743]
GSM2245188
[1744]
GSM2245189
[1745]
GSM2245190
[1746]
GSM2245191
[1747]
GSM2245192
[1748]
GSM2245193
[1749]
GSM2245194
[1750]
GSM2245195
[1751]
GSM2245196
[1752]
GSM2245197
[1753]
GSM2245198
[1754]
GSM2245199
[1755]
GSM2245200
[1756]
GSM2245201
[1757]
GSM2245202
[1758]
GSM2245203
[1759]
GSM2245204
[1760]
GSM2245205
[1761]
GSM2245206
[1762]
GSM2245207
[1763]
GSM2245208
[1764]
GSM2245209
[1765]
GSM2245210
[1766]
GSM2245211
[1767]
GSM2245212
[1768]
GSM2245213
[1769]
GSM2245214
[1770]
GSM2245215
[1771]
GSM2245216
[1772]
GSM2245217
[1773]
GSM2245218
[1774]
GSM2245219
[1775]
GSM2245220
[1776]
GSM2245221
[1777]
GSM2245222
[1778]
GSM2245223
[1779]
GSM2245224
[1780]
GSM2245225
[1781]
GSM2245226
[1782]
GSM2245227
[1783]
GSM2245228
[1784]
GSM2245229
[1785]
GSM2245230
[1786]
GSM2245231
[1787]
GSM2245232
[1788]
GSM2245233
[1789]
GSM2245234
[1790]
GSM2245235
[1791]
GSM2245236
[1792]
GSM2245237
[1793]
GSM2245238
[1794]
GSM2245239
[1795]
GSM2245240
[1796]
GSM2245241
[1797]
GSM2245242
[1798]
GSM2245243
[1799]
GSM2245244
[1800]
GSM2245245
[1801]
GSM2245246
[1802]
GSM2245247
[1803]
GSM2245248
[1804]
GSM2245249
[1805]
GSM2245250
[1806]
GSM2245251
[1807]
GSM2245252
[1808]
GSM2245253
[1809]
GSM2245254
[1810]
GSM2245255
[1811]
GSM2245256
[1812]
GSM2245257
[1813]
GSM2245258
[1814]
GSM2245259
[1815]
GSM2245260
[1816]
GSM2245261
[1817]
GSM2245262
[1818]
GSM2245263
[1819]
GSM2245264
[1820]
GSM2245265
[1821]
GSM2245266
[1822]
GSM2245267
[1823]
GSM2245268
[1824]
GSM2245269
[1825]
GSM2245270
[1826]
GSM2245271
[1827]
GSM2245272
[1828]
GSM2245273
[1829]
GSM2245274
[1830]
GSM2245275
[1831]
GSM2245276
[1832]
GSM2245277
[1833]
GSM2245278
[1834]
GSM2245279
[1835]
GSM2245280
[1836]
GSM2245281
[1837]
GSM2245282
[1838]
GSM2245283
[1839]
GSM2245284
[1840]
GSM2245285
[1841]
GSM2245286
[1842]
GSM2245287
[1843]
GSM2245288
[1844]
GSM2245289
[1845]
GSM2245290
[1846]
GSM2245291
[1847]
GSM2245292
[1848]
GSM2245293
[1849]
GSM2245294
[1850]
GSM2245295
[1851]
GSM2245296
[1852]
GSM2245297
[1853]
GSM2245298
[1854]
GSM2245299
[1855]
GSM2245300
[1856]
GSM2245301
[1857]
GSM2245302
[1858]
GSM2245303
[1859]
GSM2245304
[1860]
GSM2245305
[1861]
GSM2245306
[1862]
GSM2245307
[1863]
GSM2245308
[1864]
GSM2245309
[1865]
GSM2245310
[1866]
GSM2245311
[1867]
GSM2245312
[1868]
GSM2245313
[1869]
GSM2245314
[1870]
GSM2245315
[1871]
GSM2245316
[1872]
GSM2245317
[1873]
GSM2245318
[1874]
GSM2245319
[1875]
GSM2245320
[1876]
GSM2245321
[1877]
GSM2245322
[1878]
GSM2245323
[1879]
GSM2245324
[1880]
GSM2245325
[1881]
GSM2245326
[1882]
GSM2245327
[1883]
GSM2245328
[1884]
GSM2245329
[1885]
GSM2245330
[1886]
GSM2245331
[1887]
GSM2245332
[1888]
GSM2245333
[1889]
GSM2245334
[1890]
GSM2245335
[1891]
GSM2245336
[1892]
GSM2245337
[1893]
GSM2245338
[1894]
GSM2245339
[1895]
GSM2245340
[1896]
GSM2245341
[1897]
GSM2245342
[1898]
GSM2245343
[1899]
GSM2245344
[1900]
GSM2245345
[1901]
GSM2245346
[1902]
GSM2245347
[1903]
GSM2245348
[1904]
GSM2245349
[1905]
GSM2245350
[1906]
GSM2245351
[1907]
GSM2245352
[1908]
GSM2245353
[1909]
GSM2245354
[1910]
GSM2245355
[1911]
GSM2245356
[1912]
GSM2245357
[1913]
GSM2245358
[1914]
GSM2245359
[1915]
GSM2245360
[1916]
GSM2245361
[1917]
GSM2245362
[1918]
GSM2245363
[1919]
GSM2245364
[1920]
GSM2245365
[1921]
GSM2245366
[1922]
GSM2245367
[1923]
GSM2245368
[1924]
GSM2245369
[1925]
GSM2245370
[1926]
GSM2245371
[1927]
GSM2245372
[1928]
GSM2245373
[1929]
GSM2245374
[1930]
GSM2245375
[1931]
GSM2245376
[1932]
GSM2245377
[1933]
GSM2245378
[1934]
GSM2245379
[1935]
GSM2245380
[1936]
GSM2245381
[1937]
GSM2245382
[1938]
GSM2245383
[1939]
GSM2245384
[1940]
GSM2245385
[1941]
GSM2245386
[1942]
GSM2245387
[1943]
GSM2245388
[1944]
GSM2245389
[1945]
GSM2245390
[1946]
GSM2245391
[1947]
GSM2245392
[1948]
GSM2245393
[1949]
GSM2245394
[1950]
GSM2245395
[1951]
GSM2245396
[1952]
GSM2245397
[1953]
GSM2245398
[1954]
GSM2245399
[1955]
GSM2245400
[1956]
GSM2245401
[1957]
GSM2245402
[1958]
GSM2245403
[1959]
GSM2245404
[1960]
GSM2245405
[1961]
GSM2245406
[1962]
GSM2245407
[1963]
GSM2245408
[1964]
GSM2245409
[1965]
GSM2245410
[1966]
GSM2245411
[1967]
GSM2245412
[1968]
GSM2245413
[1969]
GSM2245414
[1970]
GSM2245415
[1971]
GSM2245416
[1972]
GSM2245417
[1973]
GSM2245418
[1974]
GSM2245419
[1975]
GSM2245420
[1976]
GSM2245421
[1977]
GSM2245422
[1978]
GSM2245423
[1979]
GSM2245424
[1980]
GSM2245425
[1981]
GSM2245426
[1982]
GSM2245427
[1983]
GSM2245428
[1984]
GSM2245429
[1985]
GSM2245430
[1986]
GSM2245431
[1987]
GSM2245432
[1988]
GSM2245433
[1989]
GSM2245434
[1990]
GSM2245435
[1991]
GSM2245436
[1992]
GSM2245437
[1993]
GSM2245438
[1994]
GSM2245439
[1995]
GSM2245440
[1996]
GSM2245441
[1997]
GSM2245442
[1998]
GSM2245443
[1999]
GSM2245444
[2000]
GSM2245445
[2001]
GSM2245446
[2002]
GSM2245447
[2003]
GSM2245448
[2004]
GSM2245449
[2005]
GSM2245450
[2006]
GSM2245451
[2007]
GSM2245452
[2008]
GSM2245453
[2009]
GSM2245454
[2010]
GSM2245455
[2011]
GSM2245456
[2012]
GSM2245457
[2013]
GSM2245458
[2014]
GSM2245459
[2015]
GSM2245460
[2016]
GSM2245461
[2017]
GSM2245462
[2018]
GSM2245463
[2019]
GSM2245464
[2020]
GSM2245465
[2021]
GSM2245466
[2022]
GSM2245467
[2023]
GSM2245468
[2024]
GSM2245469
[2025]
GSM2245470
[2026]
GSM2245471
[2027]
GSM2245472
[2028]
GSM2245473
[2029]
GSM2245474
[2030]
GSM2245475
[2031]
GSM2245476
[2032]
GSM2245477
[2033]
GSM2245478
[2034]
GSM2245479
[2035]
GSM2245480
[2036]
GSM2245481
[2037]
GSM2245482
[2038]
GSM2245483
[2039]
GSM2245484
[2040]
GSM2245485
[2041]
GSM2245486
[2042]
GSM2245487
[2043]
GSM2245488
[2044]
GSM2245489
[2045]
GSM2245490
[2046]
GSM2245491
[2047]
GSM2245492
[2048]
GSM2245493
[2049]
GSM2245494
[2050]
GSM2245495
[2051]
GSM2245496
[2052]
GSM2245497
[2053]
GSM2245498
[2054]
GSM2245499
[2055]
GSM2245500
[2056]
GSM2245501
[2057]
GSM2245502
[2058]
GSM2245503
[2059]
GSM2245504
[2060]
GSM2245505
[2061]
GSM2245506
[2062]
GSM2245507
[2063]
GSM2245508
[2064]
GSM2245509
[2065]
GSM2245510
[2066]
GSM2245511
[2067]
GSM2245512
[2068]
GSM2245513
[2069]
GSM2245514
[2070]
GSM2245515
[2071]
GSM2245516
[2072]
GSM2245517
[2073]
GSM2245518
[2074]
GSM2245519
[2075]
GSM2245520
[2076]
GSM2245521
[2077]
GSM2245522
[2078]
GSM2245523
[2079]
GSM2245524
[2080]
GSM2245525
[2081]
GSM2245526
[2082]
GSM2245527
[2083]
GSM2245528
[2084]
GSM2245529
[2085]
GSM2245530
[2086]
GSM2245531
[2087]
GSM2245532
[2088]
GSM2245533
[2089]
GSM2245534
[2090]
GSM2245535
[2091]
GSM2245536
[2092]
GSM2245537
[2093]
GSM2245538
[2094]
GSM2245539
[2095]
GSM2245540
[2096]
GSM2245541
[2097]
GSM2245542
[2098]
GSM2245543
[2099]
GSM2245544
[2100]
GSM2245545
[2101]
GSM2245546
[2102]
GSM2245547
[2103]
GSM2245548
[2104]
GSM2245549
[2105]
GSM2245550
[2106]
GSM2245551
[2107]
GSM2245552
[2108]
GSM2245553
[2109]
GSM2245554
[2110]
GSM2245555
[2111]
GSM2245556
[2112]
GSM2245557
[2113]
GSM2245558
[2114]
GSM2245559
[2115]
GSM2245560
[2116]
GSM2245561
[2117]
GSM2245562
[2118]
GSM2245563
[2119]
GSM2245564
[2120]
GSM2245565
[2121]
GSM2245566
[2122]
GSM2245567
[2123]
GSM2245568
[2124]
GSM2245569
[2125]
GSM2245570
[2126]
GSM2245571
[2127]
GSM2245572
[2128]
GSM2245573
[2129]
GSM2245574
[2130]
GSM2245575
[2131]
GSM2245576
[2132]
GSM2245577
[2133]
GSM2245578
[2134]
GSM2245579
[2135]
GSM2245580
[2136]
GSM2245581
[2137]
GSM2245582
[2138]
GSM2245583
[2139]
GSM2245584
[2140]
GSM2245585
[2141]
GSM2245586
[2142]
GSM2245587
[2143]
GSM2245588
[2144]
GSM2245589
[2145]
GSM2245590
[2146]
GSM2245591
[2147]
GSM2245592
[2148]
GSM2245593
[2149]
GSM2245594
[2150]
GSM2245595
[2151]
GSM2245596
[2152]
GSM2245597
[2153]
GSM2245598
[2154]
GSM2245599
[2155]
GSM2245600
[2156]
GSM2245601
[2157]
GSM2245602
[2158]
GSM2245603
[2159]
GSM2245604
[2160]
GSM2245605
[2161]
GSM2245606
[2162]
GSM2245607
[2163]
GSM2245608
[2164]
GSM2245609
[2165]
GSM2245610
[2166]
GSM2245611
[2167]
GSM2245612
[2168]
GSM2245613
[2169]
GSM2245614
[2170]
GSM2245615
[2171]
GSM2245616
[2172]
GSM2245617
[2173]
GSM2245618
[2174]
GSM2245619
[2175]
GSM2245620
[2176]
GSM2245621
[2177]
GSM2245622
[2178]
GSM2245623
[2179]
GSM2245624
[2180]
GSM2245625
[2181]
GSM2245626
[2182]
GSM2245627
[2183]
GSM2245628
[2184]
GSM2245629
[2185]
GSM2245630
[2186]
GSM2245631
[2187]
GSM2245632
[2188]
GSM2245633
[2189]
GSM2245634
[2190]
GSM2245635
[2191]
GSM2245636
[2192]
GSM2245637
[2193]
GSM2245638
[2194]
GSM2245639
[2195]
GSM2245640
[2196]
GSM2245641
[2197]
GSM2245642
[2198]
GSM2245643
[2199]
GSM2245644
[2200]
GSM2245645
[2201]
GSM2245646
[2202]
GSM2245647
[2203]
GSM2245648
[2204]
GSM2245649
[2205]
GSM2245650
[2206]
GSM2245651
[2207]
GSM2245652
[2208]
GSM2245653
[2209]
GSM2245654
[2210]
GSM2245655
[2211]
GSM2245656
[2212]
GSM2245657
[2213]
GSM2245658
[2214]
GSM2245659
[2215]
GSM2245660
[2216]
GSM2245661
[2217]
GSM2245662
[2218]
GSM2245663
[2219]
GSM2245664
[2220]
GSM2245665
[2221]
GSM2245666
[2222]
GSM2245667
[2223]
GSM2245668
[2224]
GSM2245669
[2225]
GSM2245670
[2226]
GSM2245671
[2227]
GSM2245672
[2228]
GSM2245673
[2229]
GSM2245674
[2230]
GSM2245675
[2231]
GSM2245676
[2232]
GSM2245677
[2233]
GSM2245678
[2234]
GSM2245679
[2235]
GSM2245680
[2236]
GSM2245681
[2237]
GSM2245682
[2238]
GSM2245683
[2239]
GSM2245684
[2240]
GSM2245685
[2241]
GSM2245686
[2242]
GSM2245687
[2243]
GSM2245688
[2244]
GSM2245689
[2245]
GSM2245690
[2246]
GSM2245691
[2247]
GSM2245692
[2248]
GSM2245693
[2249]
GSM2245694
[2250]
GSM2245695
[2251]
GSM2245696
[2252]
GSM2245697
[2253]
GSM2245698
[2254]
GSM2245699
[2255]
GSM2245700
[2256]
GSM2245701
[2257]
GSM2245702
[2258]
GSM2245703
[2259]
GSM2245704
[2260]
GSM2245705
[2261]
GSM2245706
[2262]
GSM2245707
[2263]
GSM2245708
[2264]
GSM2245709
[2265]
GSM2245710
[2266]
GSM2245711
[2267]
GSM2245712
[2268]
GSM2245713
[2269]
GSM2245714
[2270]
GSM2245715
[2271]
GSM2245716
[2272]
GSM2245717
[2273]
GSM2245718
[2274]
GSM2245719
[2275]
GSM2245720
[2276]
GSM2245721
[2277]
GSM2245722
[2278]
GSM2245723
[2279]
GSM2245724
[2280]
GSM2245725
[2281]
GSM2245726
[2282]
GSM2245727
[2283]
GSM2245728
[2284]
GSM2245729
[2285]
GSM2245730
[2286]
GSM2245731
[2287]
GSM2245732
[2288]
GSM2245733
[2289]
GSM2245734
[2290]
GSM2245735
[2291]
GSM2245736
[2292]
GSM2245737
[2293]
GSM2245738
[2294]
GSM2245739
[2295]
GSM2245740
[2296]
GSM2245741
[2297]
GSM2245742
[2298]
GSM2245743
[2299]
GSM2245744
[2300]
GSM2245745
[2301]
GSM2245746
[2302]
GSM2245747
[2303]
GSM2245748
[2304]
GSM2245749
[2305]
GSM2245750
[2306]
GSM2245751
[2307]
GSM2245752
[2308]
GSM2245753
[2309]
GSM2245754
[2310]
GSM2245755
[2311]
GSM2245756
[2312]
GSM2245757
[2313]
GSM2245758
[2314]
GSM2245759
[2315]
GSM2245760
[2316]
GSM2245761
[2317]
GSM2245762
[2318]
GSM2245763
[2319]
GSM2245764
[2320]
GSM2245765
[2321]
GSM2245766
[2322]
GSM2245767
[2323]
GSM2245768
[2324]
GSM2245769
[2325]
GSM2245770
[2326]
GSM2245771
[2327]
GSM2245772
[2328]
GSM2245773
[2329]
GSM2245774
[2330]
GSM2245775
[2331]
GSM2245776
[2332]
GSM2245777
[2333]
GSM2245778
[2334]
GSM2245779
[2335]
GSM2245780
[2336]
GSM2245781
[2337]
GSM2245782
[2338]
GSM2245783
[2339]
GSM2245784
[2340]
GSM2245785
[2341]
GSM2245786
[2342]
GSM2245787
[2343]
GSM2245788
[2344]
GSM2245789
[2345]
GSM2245790
[2346]
GSM2245791
[2347]
GSM2245792
[2348]
GSM2245793
[2349]
GSM2245794
[2350]
GSM2245795
[2351]
GSM2245796
[2352]
GSM2245797
[2353]
GSM2245798
[2354]
GSM2245799
[2355]
GSM2245800
[2356]
GSM2245801
[2357]
GSM2245802
[2358]
GSM2245803
[2359]
GSM2245804
[2360]
GSM2245805
[2361]
GSM2245806
[2362]
GSM2245807
[2363]
GSM2245808
[2364]
GSM2245809
[2365]
GSM2245810
[2366]
GSM2245811
[2367]
GSM2245812
[2368]
GSM2245813
[2369]
GSM2245814
[2370]
GSM2245815
[2371]
GSM2245816
[2372]
GSM2245817
[2373]
GSM2245818
[2374]
GSM2245819
[2375]
GSM2245820
[2376]
GSM2245821
[2377]
GSM2245822
[2378]
GSM2245823
[2379]
GSM2245824
[2380]
GSM2245825
[2381]
GSM2245826
[2382]
GSM2245827
[2383]
GSM2245828
[2384]
GSM2245829
[2385]
GSM2245830
[2386]
GSM2245831
[2387]
GSM2245832
[2388]
GSM2245833
[2389]
GSM2245834
[2390]
GSM2245835
[2391]
GSM2245836
[2392]
GSM2245837
[2393]
GSM2245838
[2394]
GSM2245839
[2395]
GSM2245840
[2396]
GSM2245841
[2397]
GSM2245842
[2398]
GSM2245843
[2399]
GSM2245844
[2400]
GSM2245845
[2401]
GSM2245846
[2402]
GSM2245847
[2403]
GSM2245848
[2404]
GSM2245849
[2405]
GSM2245850
[2406]
GSM2245851
[2407]
GSM2245852
[2408]
GSM2245853
[2409]
GSM2245854
[2410]
GSM2245855
[2411]
GSM2245856
[2412]
GSM2245857
[2413]
GSM2245858
[2414]
GSM2245859
[2415]
GSM2245860
[2416]
GSM2245861
[2417]
GSM2245862
[2418]
GSM2245863
[2419]
GSM2245864
[2420]
GSM2245865
[2421]
GSM2245866
[2422]
GSM2245867
[2423]
GSM2245868
[2424]
GSM2245869
[2425]
GSM2245870
[2426]
GSM2245871
[2427]
GSM2245872
[2428]
GSM2245873
[2429]
GSM2245874
[2430]
GSM2245875
[2431]
GSM2245876
[2432]
GSM2245877
[2433]
GSM2245878
[2434]
GSM2245879
[2435]
GSM2245880
[2436]
GSM2245881
[2437]
GSM2245882
[2438]
GSM2245883
[2439]
GSM2245884
[2440]
GSM2245885
[2441]
GSM2245886
[2442]
GSM2245887
[2443]
GSM2245888
[2444]
GSM2245889
[2445]
GSM2245890
[2446]
GSM2245891
[2447]
GSM2245892
[2448]
GSM2245893
[2449]
GSM2245894
[2450]
GSM2245895
[2451]
GSM2245896
[2452]
GSM2245897
[2453]
GSM2245898
[2454]
GSM2245899
[2455]
GSM2245900
[2456]
GSM2245901
[2457]
GSM2245902
[2458]
GSM2245903
[2459]
GSM2245904
[2460]
GSM2245905
[2461]
GSM2245906
[2462]
GSM2245907
[2463]
GSM2245908
[2464]
GSM2245909
[2465]
GSM2245910
[2466]
GSM2245911
[2467]
GSM2245912
[2468]
GSM2245913
[2469]
GSM2245914
[2470]
GSM2245915
[2471]
GSM2245916
[2472]
GSM2245917
[2473]
GSM2245918
[2474]
GSM2245919
[2475]
GSM2245920
[2476]
GSM2245921
[2477]
GSM2245922
[2478]
GSM2245923
[2479]
GSM2245924
[2480]
GSM2245925
[2481]
GSM2245926
[2482]
GSM2245927
[2483]
GSM2245928
[2484]
GSM2245929
[2485]
GSM2245930
[2486]
GSM2245931
[2487]
GSM2245932
[2488]
GSM2245933
[2489]
GSM2245934
[2490]
GSM2245935
[2491]
GSM2245936
[2492]
GSM2245937
[2493]
GSM2245938
[2494]
GSM2245939
[2495]
GSM2245940
[2496]
GSM2245941
[2497]
GSM2245942
[2498]
GSM2245943
[2499]
GSM2245945
[2500]
GSM2245948
[2501]
GSM2245950
[2502]
GSM2245952
[2503]
GSM2245955
[2504]
GSM2245957
[2505]
GSM2245959
[2506]
GSM2245961
[2507]
GSM2245965
[2508]
GSM2245966
[2509]
GSM2245968
[2510]
GSM2245971
[2511]
GSM2245972
[2512]
GSM2245974
[2513]
GSM2245976
[2514]
GSM2245977
[2515]
GSM2245980
[2516]
GSM2245981
[2517]
GSM2245982
[2518]
GSM2245983
[2519]
GSM2245984
[2520]
GSM2245985
[2521]
GSM2245986
[2522]
GSM2245987
[2523]
GSM2245988
[2524]
GSM2245989
[2525]
GSM2245990
[2526]
GSM2245991
[2527]
GSM2245992
[2528]
GSM2245993
[2529]
GSM2245994
[2530]
GSM2245995
[2531]
GSM2245996
[2532]
GSM2245997
[2533]
GSM2245998
[2534]
GSM2245999
[2535]
GSM2246000
[2536]
GSM2246001
[2537]
GSM2246002
[2538]
GSM2246003
[2539]
GSM2246004
[2540]
GSM2246005
[2541]
GSM2246006
[2542]
GSM2246007
[2543]
GSM2246008
[2544]
GSM2246009
[2545]
GSM2246010
[2546]
GSM2246011
[2547]
GSM2246012
[2548]
GSM2246013
[2549]
GSM2246014
[2550]
GSM2246015
[2551]
GSM2246016
[2552]
GSM2246017
[2553]
GSM2246018
[2554]
GSM2246019
[2555]
GSM2246020
[2556]
GSM2246021
[2557]
GSM2246022
[2558]
GSM2246023
[2559]
GSM2246024
[2560]
GSM2246025
[2561]
GSM2246026
[2562]
GSM2246027
[2563]
GSM2246028
[2564]
GSM2246029
[2565]
GSM2246030
[2566]
GSM2246031
[2567]
GSM2246032
[2568]
GSM2246033
[2569]
GSM2246034
[2570]
GSM2246035
[2571]
GSM2246036
[2572]
GSM2246037
[2573]
GSM2246038
[2574]
GSM2246039
[2575]
GSM2246040
[2576]
GSM2246041
[2577]
GSM2246042
[2578]
GSM2246043
[2579]
GSM2246044
[2580]
GSM2246045
[2581]
GSM2246046
[2582]
GSM2246047
[2583]
GSM2246048
[2584]
GSM2246049
[2585]
GSM2246050
[2586]
GSM2246051
[2587]
GSM2246052
[2588]
GSM2246053
[2589]
GSM2246054
[2590]
GSM2246055
[2591]
GSM2246056
[2592]
GSM2246057
[2593]
GSM2246058
[2594]
GSM2246059
[2595]
GSM2246060
[2596]
GSM2246061
[2597]
GSM2246062
[2598]
GSM2246063
[2599]
GSM2246064
[2600]
GSM2246065
[2601]
GSM2246066
[2602]
GSM2246067
[2603]
GSM2246068
[2604]
GSM2246069
[2605]
GSM2246070
[2606]
GSM2246071
[2607]
GSM2246072
[2608]
GSM2246073
[2609]
GSM2246074
[2610]
GSM2246075
[2611]
GSM2246076
[2612]
GSM2246077
[2613]
GSM2246078
[2614]
GSM2246079
[2615]
GSM2246080
[2616]
GSM2246081
[2617]
GSM2246082
[2618]
GSM2246083
[2619]
GSM2246084
[2620]
GSM2246085
[2621]
GSM2246086
[2622]
GSM2246087
[2623]
GSM2246088
[2624]
GSM2246089
[2625]
GSM2246090
[2626]
GSM2246091
[2627]
GSM2246092
[2628]
GSM2246093
[2629]
GSM2246094
[2630]
GSM2246095
[2631]
GSM2246096
[2632]
GSM2246097
[2633]
GSM2246098
[2634]
GSM2246099
[2635]
GSM2246100
[2636]
GSM2246101
[2637]
GSM2246102
[2638]
GSM2246103
[2639]
GSM2246104
[2640]
GSM2246105
[2641]
GSM2246106
[2642]
GSM2246107
[2643]
GSM2246108
[2644]
GSM2246109
[2645]
GSM2246110
[2646]
GSM2246111
[2647]
GSM2246112
[2648]
GSM2246113
[2649]
GSM2246114
[2650]
GSM2246115
[2651]
GSM2246116
[2652]
GSM2246117
[2653]
GSM2246118
[2654]
GSM2246119
[2655]
GSM2246120
[2656]
GSM2246121
[2657]
GSM2246122
[2658]
GSM2246123
[2659]
GSM2246124
[2660]
GSM2246125
[2661]
GSM2246126
[2662]
GSM2246127
[2663]
GSM2246128
[2664]
GSM2246129
[2665]
GSM2246130
[2666]
GSM2246131
[2667]
GSM2246132
[2668]
GSM2246133
[2669]
GSM2246134
[2670]
GSM2246135
[2671]
GSM2246136
[2672]
GSM2246137
[2673]
GSM2246138
[2674]
GSM2246139
[2675]
GSM2246140
[2676]
GSM2246141
[2677]
GSM2246142
[2678]
GSM2246143
[2679]
GSM2246144
[2680]
GSM2246145
[2681]
GSM2246146
[2682]
GSM2246147
[2683]
GSM2246148
[2684]
GSM2246149
[2685]
GSM2246150
[2686]
GSM2246151
[2687]
GSM2246152
[2688]
GSM2246153
[2689]
GSM2246154
[2690]
GSM2246155
[2691]
GSM2246156
[2692]
GSM2246157
[2693]
GSM2246158
[2694]
GSM2246159
[2695]
GSM2246160
[2696]
GSM2246161
[2697]
GSM2246162
[2698]
GSM2246163
[2699]
GSM2246164
[2700]
GSM2246165
[2701]
GSM2246166
[2702]
GSM2246167
[2703]
GSM2246168
[2704]
GSM2246169
[2705]
GSM2246170
[2706]
GSM2246171
[2707]
GSM2246172
[2708]
GSM2246173
[2709]
GSM2246174
[2710]
GSM2246175
[2711]
GSM2246176
[2712]
GSM2246177
[2713]
GSM2246178
[2714]
GSM2246179
[2715]
GSM2246180
[2716]
GSM2246181
[2717]
GSM2246182
[2718]
GSM2246183
[2719]
GSM2246184
[2720]
GSM2246185
[2721]
GSM2246186
[2722]
GSM2246187
[2723]
GSM2246188
[2724]
GSM2246189
[2725]
GSM2246190
[2726]
GSM2246191
[2727]
GSM2246192
[2728]
GSM2246193
[2729]
GSM2246194
[2730]
GSM2246195
[2731]
GSM2246196
[2732]
GSM2246197
[2733]
GSM2246198
[2734]
GSM2246199
[2735]
GSM2246200
[2736]
GSM2246201
[2737]
GSM2246202
[2738]
GSM2246203
[2739]
GSM2246204
[2740]
GSM2246205
[2741]
GSM2246206
[2742]
GSM2246207
[2743]
GSM2246208
[2744]
GSM2246209
[2745]
GSM2246210
[2746]
GSM2246211
[2747]
GSM2246212
[2748]
GSM2246213
[2749]
GSM2246214
[2750]
GSM2246215
[2751]
GSM2246216
[2752]
GSM2246217
[2753]
GSM2246218
[2754]
GSM2246219
[2755]
GSM2246220
[2756]
GSM2246221
[2757]
GSM2246222
[2758]
GSM2246223
[2759]
GSM2246224
[2760]
GSM2246225
[2761]
GSM2246226
[2762]
GSM2246227
[2763]
GSM2246228
[2764]
GSM2246229
[2765]
GSM2246230
[2766]
GSM2246231
[2767]
GSM2246232
[2768]
GSM2246233
[2769]
GSM2246234
[2770]
GSM2246235
[2771]
GSM2246236
[2772]
GSM2246237
[2773]
GSM2246238
[2774]
GSM2246239
[2775]
GSM2246240
[2776]
GSM2246241
[2777]
GSM2246242
[2778]
GSM2246243
[2779]
GSM2246244
[2780]
GSM2246245
[2781]
GSM2246246
[2782]
GSM2246247
[2783]
GSM2246248
[2784]
GSM2246249
[2785]
GSM2246250
[2786]
GSM2246251
[2787]
GSM2246252
[2788]
GSM2246253
[2789]
GSM2246254
[2790]
GSM2246255
[2791]
GSM2246256
[2792]
GSM2246257
[2793]
GSM2246258
[2794]
GSM2246259
[2795]
GSM2246260
[2796]
GSM2246261
[2797]
GSM2246262
[2798]
GSM2246263
[2799]
GSM2246264
[2800]
GSM2246265
[2801]
GSM2246266
[2802]
GSM2246267
[2803]
GSM2246268
[2804]
GSM2246269
[2805]
GSM2246270
[2806]
GSM2246271
[2807]
GSM2246272
[2808]
GSM2246273
[2809]
GSM2246274
[2810]
GSM2246275
[2811]
GSM2246276
[2812]
GSM2246277
[2813]
GSM2246278
[2814]
GSM2246279
[2815]
GSM2246280
[2816]
GSM2246281
[2817]
GSM2246282
[2818]
GSM2246283
[2819]
GSM2246284
[2820]
GSM2246285
[2821]
GSM2246286
[2822]
GSM2246287
[2823]
GSM2246288
[2824]
GSM2246289
[2825]
GSM2246290
[2826]
GSM2246291
[2827]
GSM2246292
[2828]
GSM2246293
[2829]
GSM2246294
[2830]
GSM2246295
[2831]
GSM2246296
[2832]
GSM2246297
[2833]
GSM2246298
[2834]
GSM2246299
[2835]
GSM2246300
[2836]
GSM2246301
[2837]
GSM2246302
[2838]
GSM2246303
[2839]
GSM2246304
[2840]
GSM2246305
[2841]
GSM2246306
[2842]
GSM2246307
[2843]
GSM2246308
[2844]
GSM2246309
[2845]
GSM2246310
[2846]
GSM2246311
[2847]
GSM2246312
[2848]
GSM2246313
[2849]
GSM2246314
[2850]
GSM2246315
[2851]
GSM2246316
[2852]
GSM2246317
[2853]
GSM2246318
[2854]
GSM2246319
[2855]
GSM2246320
[2856]
GSM2246321
[2857]
GSM2246322
[2858]
GSM2246323
[2859]
GSM2246324
[2860]
GSM2246325
[2861]
GSM2246326
[2862]
GSM2246327
[2863]
GSM2246328
[2864]
GSM2246329
[2865]
GSM2246330
[2866]
GSM2246331
[2867]
GSM2246332
[2868]
GSM2246333
[2869]
GSM2246334
[2870]
GSM2246335
[2871]
GSM2246336
[2872]
GSM2246337
[2873]
GSM2246338
[2874]
GSM2246339
[2875]
GSM2246340
[2876]
GSM2246341
[2877]
GSM2246342
[2878]
GSM2246343
[2879]
GSM2246344
[2880]
GSM2246345
[2881]
GSM2246346
[2882]
GSM2246347
[2883]
GSM2246348
[2884]
GSM2246349
[2885]
GSM2246350
[2886]
GSM2246351
[2887]
GSM2246352
[2888]
GSM2246353
[2889]
GSM2246354
[2890]
GSM2246355
[2891]
GSM2246356
[2892]
GSM2246357
[2893]
GSM2246358
[2894]
GSM2246359
[2895]
GSM2246360
[2896]
GSM2246361
[2897]
GSM2246362
[2898]
GSM2246363
[2899]
GSM2246364
[2900]
GSM2246365
[2901]
GSM2246366
[2902]
GSM2246367
[2903]
GSM2246368
[2904]
GSM2246369
[2905]
GSM2246370
[2906]
GSM2246371
[2907]
GSM2246372
[2908]
GSM2246373
[2909]
GSM2246374
[2910]
GSM2246375
[2911]
GSM2246376
[2912]
GSM2246377
[2913]
GSM2246378
[2914]
GSM2246379
[2915]
GSM2246380
[2916]
GSM2246381
[2917]
GSM2246382
[2918]
GSM2246383
[2919]
GSM2246384
[2920]
GSM2246385
[2921]
GSM2246386
[2922]
GSM2246387
[2923]
GSM2246388
[2924]
GSM2246389
[2925]
GSM2246390
[2926]
GSM2246391
[2927]
GSM2246392
[2928]
GSM2246393
[2929]
GSM2246394
[2930]
GSM2246395
[2931]
GSM2246396
[2932]
GSM2246397
[2933]
GSM2246398
[2934]
GSM2246399
[2935]
GSM2246400
[2936]
GSM2246401
[2937]
GSM2246402
[2938]
GSM2246403
[2939]
GSM2246404
[2940]
GSM2246405
[2941]
GSM2246406
[2942]
GSM2246407
[2943]
GSM2246408
[2944]
GSM2246409
[2945]
GSM2246410
[2946]
GSM2246411
[2947]
GSM2246412
[2948]
GSM2246413
[2949]
GSM2246414
[2950]
GSM2246415
[2951]
GSM2246416
[2952]
GSM2246417
[2953]
GSM2246418
[2954]
GSM2246419
[2955]
GSM2246420
[2956]
GSM2246421
[2957]
GSM2246422
[2958]
GSM2246423
[2959]
GSM2246424
[2960]
GSM2246425
[2961]
GSM2246426
[2962]
GSM2246427
[2963]
GSM2246428
[2964]
GSM2246429
[2965]
GSM2246430
[2966]
GSM2246431
[2967]
GSM2246432
[2968]
GSM2246433
[2969]
GSM2246434
[2970]
GSM2246435
[2971]
GSM2246436
[2972]
GSM2246437
[2973]
GSM2246438
[2974]
GSM2246439
[2975]
GSM2246440
[2976]
GSM2246441
[2977]
GSM2246442
[2978]
GSM2246443
[2979]
GSM2246444
[2980]
GSM2246445
[2981]
GSM2246446
[2982]
GSM2246447
[2983]
GSM2246448
[2984]
GSM2246449
[2985]
GSM2246450
[2986]
GSM2246451
[2987]
GSM2246452
[2988]
GSM2246453
[2989]
GSM2246454
[2990]
GSM2246455
[2991]
GSM2246456
[2992]
GSM2246457
[2993]
GSM2246458
[2994]
GSM2246459
[2995]
GSM2246460
[2996]
GSM2246461
[2997]
GSM2246462
[2998]
GSM2246463
[2999]
GSM2246464
[3000]
GSM2246465
[3001]
GSM2246466
[3002]
GSM2246467
[3003]
GSM2246468
[3004]
GSM2246469
[3005]
GSM2246470
[3006]
GSM2246471
[3007]
GSM2246472
[3008]
GSM2246473
[3009]
GSM2246474
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sample_count
3589
group_sizes
null
group_sizes_basis
null
platform
18573
taxon
Homo sapiens
title
Single-Cell RNAseq analysis of diffuse neoplastic infiltrating cells at the migrating front of human glioblastoma
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 2 items
[0]
asset:data:geo:GSE84465 not downloaded
[1]
asset:data:geo:GSE84465 licence not read
analysis object · 4 fields
state
partial
methods array · 1 item
[0] object · 10 fields
id
method-1
family
null
specific
null
label
unsupervised clustering
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
Then, we used the R package “Seurat” to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
blocked
tier
R4
blocking_axis
method
blocked_on
method:not_determinable
axes object · 3 fields
method object · 5 fields
tier
R4
expressible
false
required_operations array · 0 items
missing_operations array · 0 items
basis
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We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing.
basis
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is mostly performed based on transcriptome (RNA-seq) without considering lncRNA molecules that a
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33693962", "kind": "science-record", "revision": 3, "content_hash": "sha256:17fb398d2cd20c8ea4abf22b9b6f62ecd3c32258eb9f101a1a35ec5e0e3138f3", "created_at": "2026-11-01T17:34:53Z", "updated_at": "2026-11-01T21:24:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "New insights for precision treatment of glioblastoma from analysis of single-cell lncRNA expression.", "doi": "10.1007/s00432-021-03584-9", "pmid": "33693962", "authors": ["Qingkang Meng", "Yan Zhang", "Guoqi Li", "Yunong Li", "Hongbo Xie", "Xiujie Chen"], "journal": "Journal of cancer research and clinical oncology", "year": 2021, "abstract": "INTRODUCTION: Glioblastoma (GBM) is a complex disease with high intratumoral heterogeneity, understanding the molecular characteristics of intratumoral heterogeneity accurately is the basis for precision treatment. Although the existing typing strategy based on tumor molecular characteristics has a positive effect, there is still room for improvement, which is mainly because the traditional typing is completed based on the sequencing data of tissue samples, that is, the obtained data are the average level of patient tumor tissues, masking the intratumoral heterogeneity of a single patient and cannot reflect the real level of patient tumor cells. At present, cancer molecular typing is mostly performed based on transcriptome (RNA-seq) without considering lncRNA molecules that are also tissue-specific and developmental stage-specific. Therefore, in this study, we used lncRNAs as typing markers and combined single-cell expression profiles to retype glioblastoma, providing new ideas for GBM molecular typing, and further analyzed the shortcomings of traditional therapies at the singlecell level based on typing results and proposed new precise therapeutic insights.\nMETHODS: We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing. The intratumoral heterogeneity of patients at the single-cell level was revealed using t-SNE, and the room for improvement of the existing traditional histotyping method was revealed using heat map and density curve. Subsequently, to validate the feasibility of lncRNA typing, we compared the similarities and differences of expression patterns between lncRNAs and mRNAs in GBM cells. Then, we used the R package \"Seurat\" to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs. For validation, we performed survival analysis on GBM tissue data from the TCGA database to reveal the impact of different subtypes on patient survival prognosis. Eventually, based on the results, we screened the therapeutic drugs of each subtype by targeting the downstream regulatory genes of lncRNAs and proposed a new precision therapeutic strategy.\nRESULTS: GBM has significant intratumoral heterogeneity at the single-cell level, with more than one traditional subtype highly expressed in each patient, which reflects the shortcomings of traditional histotyping. LncRNAs and mRNAs have similar expression patterns in GBM cells, and the expression coefficient of variation of lncRNAs is higher than that of mRNAs, meaning that lncRNAs will better reflect the intratumoral heterogeneity. GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics. Survival analysis showed that patients with different subtype compositions had different prognostic outcomes, so different subtypes had different effects on patient prognosis. Based on this, 47 drugs were screened for treatment. There are both shared and unique drugs between different subtypes. A new precision treatment strategy was proposed: for patients with different subtypes, in addition to the combination of drugs targeting single subtype, drugs targeting multiple subtypes can also be selected.\nCONCLUSION: Intratumoral heterogeneity may lead to poor prognosis or recurrence after treatment, and more precise typing of GBM can be performed based on single-cell lncRNA expression profiles. The biological characteristics possessed by different subtypes will have different effects on patients, such as survival time. For different subtypes, there are both drugs targeting single subtype and drugs targeting multiple subtypes, and we prefer drugs targeting multiple subtypes because this strategy can maximize medication efficiency and reduce the types of medication to reduce risks and side effects.", "claims": [{"id": "claim-method", "statement": "Then, we used the R package “Seurat” to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33693962", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Then, we used the R package “Seurat” to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33693962", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing."}], "state": "complete"}, {"id": "claim-target-result", "statement": "GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:33693962", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33693962"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE84465"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE84465"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33693962", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s00432-021-03584-9", "sha256": 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"GSM2244563", "GSM2244564", "GSM2244565", "GSM2244566", "GSM2244567", "GSM2244568", "GSM2244569", "GSM2244570", "GSM2244571", "GSM2244572", "GSM2244573", "GSM2244574", "GSM2244575", "GSM2244576", "GSM2244577", "GSM2244578", "GSM2244579", "GSM2244580", "GSM2244581", "GSM2244582", "GSM2244583", "GSM2244584", "GSM2244585", "GSM2244586", "GSM2244587", "GSM2244588", "GSM2244589", "GSM2244590", "GSM2244591", "GSM2244592", "GSM2244593", "GSM2244594", "GSM2244595", "GSM2244596", "GSM2244597", "GSM2244598", "GSM2244599", "GSM2244600", "GSM2244601", "GSM2244602", "GSM2244603", "GSM2244604", "GSM2244605", "GSM2244606", "GSM2244607", "GSM2244608", "GSM2244609", "GSM2244610", "GSM2244611", "GSM2244612", "GSM2244613", "GSM2244614", "GSM2244615", "GSM2244616", "GSM2244617", "GSM2244618", "GSM2244619", "GSM2244620", "GSM2244621", "GSM2244622", "GSM2244623", "GSM2244624", "GSM2244625", "GSM2244626", "GSM2244627", "GSM2244628", "GSM2244629", "GSM2244630", "GSM2244631", "GSM2244632", "GSM2244633", 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"GSM2245770", "GSM2245771", "GSM2245772", "GSM2245773", "GSM2245774", "GSM2245775", "GSM2245776", "GSM2245777", "GSM2245778", "GSM2245779", "GSM2245780", "GSM2245781", "GSM2245782", "GSM2245783", "GSM2245784", "GSM2245785", "GSM2245786", "GSM2245787", "GSM2245788", "GSM2245789", "GSM2245790", "GSM2245791", "GSM2245792", "GSM2245793", "GSM2245794", "GSM2245795", "GSM2245796", "GSM2245797", "GSM2245798", "GSM2245799", "GSM2245800", "GSM2245801", "GSM2245802", "GSM2245803", "GSM2245804", "GSM2245805", "GSM2245806", "GSM2245807", "GSM2245808", "GSM2245809", "GSM2245810", "GSM2245811", "GSM2245812", "GSM2245813", "GSM2245814", "GSM2245815", "GSM2245816", "GSM2245817", "GSM2245818", "GSM2245819", "GSM2245820", "GSM2245821", "GSM2245822", "GSM2245823", "GSM2245824", "GSM2245825", "GSM2245826", "GSM2245827", "GSM2245828", "GSM2245829", "GSM2245830", "GSM2245831", "GSM2245832", "GSM2245833", "GSM2245834", "GSM2245835", "GSM2245836", "GSM2245837", "GSM2245838", "GSM2245839", "GSM2245840", 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