BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance
Ielizaveta Gorodetska1, Iryna Kozeretska2, Anna Dubrovska3
1OncoRay-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.
Abstract:
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.
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