Journal
JOURNAL OF CANCER
Volume 10, Issue 9, Pages 2109-2127Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.30410
Keywords
BRCA1; BRCA2; genomic instability; cancer stem cells; cancer treatment
Categories
Funding
- German Academic Exchange Service (DAAD)
- Federation of European Biochemical Societies (FEBS)
- Deutsche Forschungsgemeinschaft (DFG) [273676790, 416001651, 4013263 37]
- Wilhelm Sander-Stiftung [2017.106.1]
- BMBF [03Z1NN11]
- DLR Project Management Agency [01DK17047]
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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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