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pmid:26556035

TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.

Anne M Schultheis · Luciano G Martelotto · Maria R De Filippo · Salvatore Piscuglio · Charlotte K Y Ng · Yaser R Hussein · Jorge S Reis-Filho · Robert A Soslow · Britta Weigelt

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2016 doi:10.1097/PGP.0000000000000243

Paper

complete

Experiment

partial

Data

partial

Analysis

complete

Execution

absent

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TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.
doi
10.1097/PGP.0000000000000243
pmid
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Anne M Schultheis
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Luciano G Martelotto
[2]
Maria R De Filippo
[3]
Salvatore Piscuglio
[4]
Charlotte K Y Ng
[5]
Yaser R Hussein
[6]
Jorge S Reis-Filho
[7]
Robert A Soslow
[8]
Britta Weigelt
journal
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
year
2016
abstract
Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient.
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Whilst 63% of all TP53-mutant EECs displayed a PTEN somatic mutation, only 3% of TP53-mutant SECs harbored somatic mutations affecting this gene (Fisher’s exact test p<0.0001; Supplemental Table 4).
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Within the subset of TP53-mutant ECs, a significant association between histologic type and PTEN mutations was identified (Table 1).
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Whilst 63% of all TP53-mutant EECs displayed a PTEN somatic mutation, only 3% of TP53-mutant SECs harbored somatic mutations affecting this gene (Fisher’s exact test p<0.0001; Supplemental Table 4).
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The study re-analyzed publicly available The Cancer Genome Atlas endometrial carcinoma data obtained through cBioPortal and used two-tailed Fisher’s exact or Chi-square tests for group comparisons; its headline association was that TP53-mutant endometrioid carcinomas more frequently harbored PTEN mutations than TP53-mutant serous carcinomas.
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