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Genomic mutation features identify distinct BRCA-associated mutation characteristics in endometrioid carcinoma and endometrioid ovarian carcinoma
- Source :
- Aging (Albany NY)
- Publication Year :
- 2021
- Publisher :
- Impact Journals, 2021.
-
Abstract
- Although endometrioid carcinoma (EC) and endometrioid ovarian carcinoma (EnOC) display similar pathological features, their molecular characteristics remain to be determined. Somatic mutation data from 2777 EC, 423 EnOC, and 57 endometriosis patients from the Catalogue of Somatic Mutations in Cancer (COSMIC) dataset were analyzed and showed similar profiles with different mutation frequencies among them. By using 275 overlapping mutated genes, EC was clustered into two groups with different disease outcomes and different clinical characteristics. Although BRCA-associated mutation characteristics were identified in both EC and EnOC, the mutation frequencies of BRCA1 (P=0.0146), BRCA2 (P=0.0321), ATR (P=3.25E-11), RAD51 (P=3.95E-08), RAD1 (P=0.0003), TP53 (P=6.11E-33), and BRIP1 (P=2.90E-09) were higher in EnOC. Further analysis showed that EnOC cell lines with BRCA-associated mutation characteristics were more sensitive to poly ADP-ribose polymerase (PARP) inhibitors than EC cell lines, including olaparib, talazoparib, rucaparib, and veliparib. Moreover, based on BRCA-associated mutational and transcriptomic profiles, EC with BRCA-associated mutational burdens shows lower levels of immune cell infiltration, higher expression of immunosuppressive checkpoint molecules and worse prognosis than EC without BRCA mutation. Our study comprehensively analyzed the genome mutation features of EC and EnOC and provide insights into the molecular characteristics of EC and EnOC.
- Subjects :
- Aging
Veliparib
endocrine system diseases
endometrioid ovarian carcinoma
genome mutation
BRCA
Biology
immune response
Olaparib
chemistry.chemical_compound
Germline mutation
Ovarian carcinoma
Carcinoma
medicine
Humans
Rucaparib
BRCA2 Protein
Ovarian Neoplasms
BRCA1 Protein
BRCA mutation
Cell Biology
medicine.disease
Endometrial Neoplasms
chemistry
Mutation (genetic algorithm)
Mutation
Cancer research
Female
Transcriptome
Carcinoma, Endometrioid
Research Paper
endometrioid carcinoma
Subjects
Details
- Language :
- English
- ISSN :
- 19454589
- Volume :
- 13
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY)
- Accession number :
- edsair.doi.dedup.....1d76e6a077d2fafcf92917cca0b36bc9