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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
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Experiment
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Data
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Analysis
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Complete file
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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.", "claims": [{"id": "claim-target-result", "statement": "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.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "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)."}, "evidence": [{"asset": "source:pmid:26556035", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Here we sought to define the frequency, pattern, distribution and type of TP53 somatic mutations in ECs by performing a re-analysis of the publicly available data from The Cancer Genome Atlas (TCGA)."}, {"asset": "source:pmid:26556035", "locator": "sections[10] \"Associations between highly recurrently mutated genes in ECs and TP53 mutational status\" paragraph 5", "quote": "Within the subset of TP53-mutant ECs, a significant association between histologic type and PTEN mutations was identified (Table 1)."}, {"asset": "source:pmid:26556035", "locator": "sections[10] \"Associations between highly recurrently mutated genes in ECs and TP53 mutational status\" paragraph 5", "quote": "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)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "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.", "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:26556035"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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