BRCA Genes: The Role in Genome Stability, Cancer Sternness and Therapy Resistance

被引：139

作者：

Gorodetska, Ielizaveta ^{[1
,2
,3
]}

Kozeretska, Iryna ^{[4
]}

Dubrovska, Anna ^{[1
,2
,5
,6
,7
]}

机构：

[1] Tech Univ Dresden, Fac Med, OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany

[2] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[3] Helmholtz Zentrum Dresden Rossendorf, Dresden, Germany

[4] Taras Shevchenko Natl Univ Kyiv, ESC Inst Biol & Med, Dept Gen & Med Genet, Kiev, Ukraine

[5] Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol OncoRay, Dresden, Germany

[6] German Canc Consortium DKTK, Partner Site Dresden, Dresden, Germany

[7] German Canc Res Ctr, Heidelberg, Germany

来源：

JOURNAL OF CANCER | 2019年 / 10卷 / 09期

关键词：

BRCA1; BRCA2; genomic instability; cancer stem cells; cancer treatment; DNA-DAMAGE RESPONSE; ESTROGEN-RECEPTOR-ALPHA; NEGATIVE BREAST-CANCER; ACUTE MYELOID-LEUKEMIA; GERM-LINE MUTATIONS; CELL-CYCLE ARREST; OVARIAN-CANCER; STEM-CELLS; HOMOLOGOUS RECOMBINATION; TUMOR-SUPPRESSOR;

D O I：

10.7150/jca.30410

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2109 / 2127

页数：19

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