Landscape of chromatin remodeling gene alterations in endometrial carcinoma.
Chromatin remodeling
DNA, endometrial carcinoma
Genetics
Massively parallel sequencing
Mutations
RNA, SWI/SNF
Transcriptomics
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
13
11
2022
revised:
01
02
2023
accepted:
15
03
2023
pmc-release:
01
05
2024
medline:
19
5
2023
pubmed:
24
3
2023
entrez:
23
3
2023
Statut:
ppublish
Résumé
Chromatin remodeling genes (CRGs) encode components of epigenetic regulatory mechanisms and alterations in these genes have been identified in several tumor types, including gynecologic cancers. In this study, we sought to investigate the prevalence and clinicopathological associations of CRG alterations in endometrial carcinoma (EC). We performed a retrospective analysis of 660 ECs sequenced using a clinical massively parallel sequencing assay targeting up to 468 genes, including 25 CRGs, and defined the presence of somatic CRG alterations. Clinicopathologic features were obtained for all cases. Immunohistochemical interrogation of ARID1A and PTEN proteins was performed in a subset of samples. Of the 660 ECs sequenced, 438 (66.4%) harbored CRG alterations covered by our panel. The most commonly altered CRG was ARID1A (46%), followed by CTCF (21%), KMT2D (18%), KMT2B (17%), BCOR (16%), ARID1B (12%) and SMARCA4 (11%). We found that ARID1A genetic alterations were preferentially bi-allelic and often corresponded to altered ARID1A protein expression in ECs. We further observed that ARID1A alterations were often subclonal when compared to PTEN alterations, which were primarily clonal in ECs harboring both mutations. Finally, CRG alterations were associated with an increased likelihood of myometrial and lymphovascular invasion in endometrioid ECs. CRG alterations are common in EC and are associated with clinicopathologic features and likely play a crucial role in EC.
Identifiants
pubmed: 36958196
pii: S0090-8258(23)00145-2
doi: 10.1016/j.ygyno.2023.03.010
pmc: PMC10192087
mid: NIHMS1884502
pii:
doi:
Substances chimiques
Chromatin
0
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Nuclear Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
54-64Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest B.W. reports ad hoc membership of the scientific advisory board of REPARE Therapeutics, outside the current work. R.A.S. reports medical legal consultant (Shook Hardy Bacon); royalties from Modern Pathology/USCAP, AFIP/ARP, Cambridge Univ Press and Springer publishing. C.A. reports membership of advisory boards/ personal fees from Tesaro, Eisai/Merck, Mersana Therapeutics, Roche/Genentech, Abbvie, AstraZeneca/Merck, Repare Therapeutics, and grants from Clovis, Genentech, AbbVie, Astra Zeneca, all outside the submitted work. N.R. Abu-Rustum reports Stryker/ Novadaq and GRAIL grants paid to the institution, outside the current study. The remaining authors have no relevant conflicts.
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