TP53 mutational spectrum in endometrioid and serous endometrial cancers Journal Article

   


Authors: Schultheis, A. M.; Martelotto, L. G.; De Filippo, M. R.; Piscuoglio, S.; Ng, C. K. Y.; Hussein, Y. R.; Reis, J. S.; Soslow, R. A.; Weigelt, B.
Article Title: TP53 mutational spectrum in endometrioid and serous endometrial cancers
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.
Keywords: immunohistochemistry; classification; carcinoma; pten; endometrial carcinoma; features; strategies; pathway; subtype; histologic; tp53 mutation; high-frequency; mutant p53; hotspot mutation; genomic subtype; fbxw7
Journal Title: International Journal of Gynecological Pathology
Volume: 35
Issue: 4
ISSN: 0277-1691
Publisher: Lippincott Williams & Wilkins  
Date Published: 2016-07-01
Start Page: 289
End Page: 300
Language: English
ACCESSION: WOS:000377619500001
DOI: 10.1097/pgp.0000000000000243
PROVIDER: wos
PUBMED: 26556035
PMCID: PMC5087968
Notes: Article -- Source: Wos
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MSK Authors
  1. Robert Soslow
    793 Soslow
  2. Yaser Raji Hussein
    45 Hussein
  3. Britta Weigelt
    632 Weigelt
  4. Jorge Sergio Reis-Filho
    639 Reis-Filho
  5. Kiu Yan Charlotte Ng
    155 Ng
  6. Salvatore Piscuoglio
    130 Piscuoglio
  7. Luciano Gaston Martelotto
    69 Martelotto
  8. Anne Maria Schultheis
    38 Schultheis
  9. Maria Rosaria De Filippo
    28 De Filippo
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