Journal of ISSN: 2373-4469JIG

Investigative Genomics
Volume 2 Issue 5 - 2015
BRCA1 Expression Regulation and its Role as a Biomarker of Cancer
Elena A Shestakova*
N.N. Blokhin Russian Cancer Research Center, Russian Federation
Received: October 21, 2015 | Published: November 4, 2015
*Corresponding author: Elena A. Shestakova, Federal State Budgetary Scientific Institution “N.N.Blokhin Russian Cancer Research Center” of the Ministry of Health of the Russian Federation, Kashirskoe shosse 24, 115478, Moscow, Russian Federation, Tel: +7499 612 8072; Email:
Citation: Shestakova EA (2015) BRCA1 Expression Regulation and its Role as a Biomarker of Cancer. J Investig Genomics 2(5): 00037. DOI: 10.15406/jig.2015.02.00037


Tumor suppressor BRCA1 prevents the development of several cancers, mainly breast and ovarian cancer. The main function of BRCA1 is the repair of DNA damage through homology recombination [1,2]. The disruption of this BRCA1 function leads to the development of several oncological diseases, in particular, breast cancer, ovarian cancer and also non-small cell lung cancer. Recently, it became clear that BRCA1 can serve as a prognostic marker of the course of several oncological diseases and as a predictive marker of platinum-based therapy.

Since the discovery of BRCA1 in early 1990 extensive studies of its biological function and mechanisms of its expression were carried out. Together with its associated proteins BRCA1 is involved in the repair of DNA double strand breaks through homologous recombination mechanism [2]. Fine tuning of BRCA1 protein level is important for its balanced function in homologous recombination and therefore in the maintenance of genomic stability. Several molecular mechanisms of BRCA1 gene alterations and BRCA1 gene expression regulation were revealed. These mechanisms include germinal and sporadic mutations in BRCA1 gene [3], epigenetic mechanisms of the disruption of BRCA1 gene expression including methylation of CpG islands [4,5] and covalent histone modifications in the promoter and coding region of BRCA1 gene, regulation with transcription factors [6], loss of one allele of BRCA1 gene (so called loss of heterozigosity, LOH) [7] and possibly amplification of BRCA1 gene [8]. It has been demonstrated that these mechanisms could be the cause of BRCA1 function disruption and further could lead to the development of cancer.

In addition to well studied biological function of BRCA1 in homologous recombination and mechanisms of regulation of its expression, recently the role of BRCA1 as a biomarker of several oncological diseases emerged. It was shown that decreased levels of BRCA1 protein and mRNA often correlated with the development of breast and ovarian cancer and that the level of BRCA1 protein and mRNA could predict favorable/unfavorable course of the disease [9]. Therefore, BRCA1 could function as a prognostic marker of the disease course. Moreover, it was demonstrated that decreased levels of BRCA1 protein and mRNA correlated with decreased resistance to platinum-based chemotherapy [10-12]. Therefore, BRCA1 could be a predictive marker of platinum chemotherapy efficiency.

Taken together, BRCA1 perfectly corresponds to the definition of the biomarker. The biomarker has three main characteristics that include, first of all, a defined biological function, second, quantitative methods of its detection and third, the availability of patient cohorts of reasonable size to be studied. Firstly, it has defined biological function participating in the repair of DNA double strand breaks via homologous recombination. Secondly, there are several very precise methods allowing to measure quantities of BRCA1 protein and mRNA. Thirdly, patient cohorts of reasonable size are available for analysis. Altogether, BRCA1 protein emerges in recent years as the prognostic marker of the course of oncological diseases and as the predictive marker of the efficiency of platinum-based chemotherapy that is extensively used in the treatment of BRCA1-dependent cancers.


Dr. Elena A. Shestakova holds a position of Senior Research Scientist, PhD at N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.


  1. Moynahan ME, Chiu JW, Koller BH, Jasin M (1999) Brca1 controls homology-directed DNA repair. Mol Cell 4(4): 511-518.
  2. Jiang Q, Greenberg RA (2015) Deciphering the BRCA1 tumor suppressor network. J Biol Chem 290(29): 17724-17732.
  3. Wong-Brown MW, Meldrum CJ, Carpenter JE, Clarke CL, Narod SA, et al. (2015) Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Breast Cancer Res Treat 150(1): 71-80.
  4. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, et al. (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 92(7): 564-569.
  5. Wong EM, Southey MC, Fox SB, Brown MA, Dowty JG, et al. (2011) Constitutional methylation of the BRCA1 promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer. Cancer Prev Res 4(1): 23-33.
  6. McCoy ML, Mueller CR, Roskelley CD (2003) The role of the breast cancer susceptibility gene 1 (BRCA1) in sporadic epithelial ovarian cancer. Reproductive Biol Endocrinol 1: 1-5.
  7. Russel PA, Pharoah PD, De Foy K, Ramus SJ, Symmonds I, et al. (2000) Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers. Int J Cancer 87(3): 317-321.
  8. Ribeiro IP, Marques F, Caramelo F, Pereira J, Patricio M, et al. (2014) Genetic gains and losses in oral squamous cell carcinoma: impact on clinical management. Cell Oncol 37(1): 29-39.
  9. Thrall M, Gallion HH, Kryscio R, Kapali M, Armstrong DK, et al. (2006) BRCA1 expression in a large series of sporadic ovarian carcinomas: a Gynecologic Oncology Group study. Int J Gynecol Cancer 16(Suppl 1): 166-171.
  10. Carser JE, Quinn JE, Michie CO, O`Brien EJ, McCluggage WG, et al. (2011) BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer. Gynecol Oncol 123(3): 492-498.
  11. Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, et al. (2011) Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study. Ann Oncol 22(11): 2403-2410.
  12. Byrski T, Huzarski T, Dent R, Marczyk E, Jasiowka M, et al. (2014) Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 147(2): 401-405.
© 2014-2016 MedCrave Group, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use.
Creative Commons License Open Access by MedCrave Group is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at
Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version | Opera |Privacy Policy