1. Transcriptome Patterns of BRCA1- and BRCA2- Mutated Breast and Ovarian Cancers
- Author
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Siras Hakobyan, U. A. Boyarskih, Maxim L. Filipenko, Maria Nikoghosyan, Lilit Nersisyan, Ani Melkonyan, Arman Simonyan, Arsen Arakelyan, and Hans Binder
- Subjects
endocrine system diseases ,Somatic cell ,Poly (ADP-Ribose) Polymerase-1 ,medicine.disease_cause ,transcriptome portrayal ,Germline ,Transcriptome ,lcsh:Chemistry ,Antineoplastic Combined Chemotherapy Protocols ,skin and connective tissue diseases ,lcsh:QH301-705.5 ,Spectroscopy ,Ovarian Neoplasms ,Mutation ,BRCA1 Protein ,somatic and germline mutations ,General Medicine ,Middle Aged ,Phenotype ,female genital diseases and pregnancy complications ,Computer Science Applications ,BRCA1 ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,ovarian cancer ,Female ,Poly(ADP-ribose) Polymerases ,BRCA2 ,Adult ,multi-layer self-organizing maps ,Breast Neoplasms ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,Breast cancer ,Germline mutation ,breast cancer ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,BRCA2 Protein ,Gene Expression Profiling ,Organic Chemistry ,Computational Biology ,medicine.disease ,Survival Analysis ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cancer research ,Ovarian cancer - Abstract
Mutations in the BRCA1 and BRCA2 genes are known risk factors and drivers of breast and ovarian cancers. So far, few studies have been focused on understanding the differences in transcriptome and functional landscapes associated with the disease (breast vs. ovarian cancers), gene (BRCA1 vs. BRCA2), and mutation type (germline vs. somatic). In this study, we were aimed at systemic evaluation of the association of BRCA1 and BRCA2 germline and somatic mutations with gene expression, disease clinical features, outcome, and treatment. We performed BRCA1/2 mutation centered RNA-seq data analysis of breast and ovarian cancers from the TCGA repository using transcriptome and phenotype &ldquo, portrayal&rdquo, with multi-layer self-organizing maps and functional annotation. The results revealed considerable differences in BRCA1- and BRCA2-dependent transcriptome landscapes in the studied cancers. Furthermore, our data indicated that somatic and germline mutations for both genes are characterized by deregulation of different biological functions and differential associations with phenotype characteristics and poly(ADP-ribose) polymerase (PARP)-inhibitor gene signatures. Overall, this study demonstrates considerable variation in transcriptomic landscapes of breast and ovarian cancers associated with the affected gene (BRCA1 vs. BRCA2), as well as the mutation type (somatic vs. germline). These results warrant further investigations with larger groups of mutation carriers aimed at refining the understanding of molecular mechanisms of breast and ovarian cancers.
- Published
- 2021
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