Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: review of radiosensitivity assays

Biological Procedures Online

Nahid Karkhaneh Yousefi¹  Tahereh Azari²  Maral Ranjbar²  Mojdeh Matloubi²  Fatemeh Sadeghi³  Majid Zaki-Dizaji⁴  Marzieh Asgari⁵ 

[1] Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran;Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;Digestive Diseases Research Institute, Digestive Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran;Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran;Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;Rheumatology Research Center, Tehran University of Medical Sciences, Shariati Hospital, Kargar Ave, Tehran, Iran;

关键词: BRCA1;    BRCA2;    breast cancer;    genome stability;    radiosensitivity;    DNA repair pathway;    cell cycle;    apoptosis;    homologous recombination;    non-homologous end joining;   

DOI  :  10.1186/s12575-020-00133-5

来源: Springer

【 摘 要 】

BackgroundDNA repair pathways, cell cycle arrest checkpoints, and cell death induction are present in cells to process DNA damage and prevent genomic instability caused by various extrinsic and intrinsic ionizing factors. Mutations in the genes involved in these pathways enhances the ionizing radiation sensitivity, reduces the individual’s capacity to repair DNA damages, and subsequently increases susceptibility to tumorigenesis.BodyBRCA1 and BRCA2 are two highly penetrant genes involved in the inherited breast cancer and contribute to different DNA damage pathways and cell cycle and apoptosis cascades. Mutations in these genes have been associated with hypersensitivity and genetic instability as well as manifesting severe radiotherapy complications in breast cancer patients. The genomic instability and DNA repair capacity of breast cancer patients with BRCA1/2 mutations have been analyzed in different studies using a variety of assays, including micronucleus assay, comet assay, chromosomal assay, colony-forming assay, γ -H2AX and 53BP1 biomarkers, and fluorescence in situ hybridization. The majority of studies confirmed the enhanced spontaneous & radiation-induced radiosensitivity of breast cancer patients compared to healthy controls. Using G2 micronucleus assay and G2 chromosomal assay, most studies have reported the lymphocyte of healthy carriers with BRCA1 mutation are hypersensitive to invitro ionizing radiation compared to non-carriers without a history of breast cancer. However, it seems this approach is not likely to be useful to distinguish the BRCA carriers from non-carrier with familial history of breast cancer.ConclusionIn overall, breast cancer patients are more radiosensitive compared to healthy control; however, inconsistent results exist about the ability of current radiosensitive techniques in screening BRCA1/2 carriers or those susceptible to radiotherapy complications. Therefore, developing further radiosensitivity assay is still warranted to evaluate the DNA repair capacity of individuals with BRCA1/2 mutations and serve as a predictive factor for increased risk of cancer mainly in the relatives of breast cancer patients. Moreover, it can provide more evidence about who is susceptible to manifest severe complication after radiotherapy.

【 授权许可】

CC BY