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Transcriptome Patterns of <i>BRCA1</i>- and <i>BRCA2</i>- Mutated Breast and Ovarian Cancers
oleh: Arsen Arakelyan, Ani Melkonyan, Siras Hakobyan, Uljana Boyarskih, Arman Simonyan, Lilit Nersisyan, Maria Nikoghosyan, Maxim Filipenko, Hans Binder
Format: | Article |
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Diterbitkan: | MDPI AG 2021-01-01 |
Deskripsi
Mutations in the <i>BRCA1</i> and <i>BRCA2</i> 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 (<i>BRCA1</i> vs. <i>BRCA2</i>), and mutation type (germline vs. somatic). In this study, we were aimed at systemic evaluation of the association of <i>BRCA1</i> and <i>BRCA2</i> germline and somatic mutations with gene expression, disease clinical features, outcome, and treatment. We performed <i>BRCA1/2</i> mutation centered RNA-seq data analysis of breast and ovarian cancers from the TCGA repository using transcriptome and phenotype “portrayal” with multi-layer self-organizing maps and functional annotation. The results revealed considerable differences in <i>BRCA1</i>- and <i>BRCA2</i>-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 (<i>BRCA1</i> vs. <i>BRCA2</i>), 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.