J Cancer 2019; 10(9):2109-2127. doi:10.7150/jca.30410
BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance
1. OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany;
2. Department of General and Medical Genetics, ESC "The Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv, Ukraine;
3. OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; German Cancer Consortium (DKTK), Partner site Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Gorodetska I, Kozeretska I, Dubrovska A. BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. J Cancer 2019; 10(9):2109-2127. doi:10.7150/jca.30410. Available from https://www.jcancer.org/v10p2109.htm
Carcinogenesis is a multistep process, and tumors frequently harbor multiple mutations regulating genome integrity, cell division and death. The integrity of cellular genome is closely controlled by the mechanisms of DNA damage signaling and DNA repair. The association of breast cancer susceptibility genes BRCA1 and BRCA2 with breast and ovarian cancer development was first demonstrated over 20 years ago. Since then the germline mutations within these genes were linked to genomic instability and increased risk of many other cancer types. Genomic instability is an engine of the oncogenic transformation of non-tumorigenic cells into tumor-initiating cells and further tumor evolution. In this review we discuss the biological functions of BRCA1 and BRCA2 genes and the role of BRCA mutations in tumor initiation, regulation of cancer stemness, therapy resistance and tumor progression.
Keywords: BRCA1, BRCA2, genomic instability, cancer stem cells, cancer treatment