Top

Published in:

01-04-2012 | Viewpoint

BRCA1 as a tumor suppressor linked to the regulation of epigenetic states: keeping oncomiRs under control

Authors: Olafur Andri Stefansson, Manel Esteller

Published in: Breast Cancer Research | Issue 2/2012

Abstract

BRCA1 is a tumor suppressor gene known to be implicated in the development of a subset of breast and ovarian cancers. The tumor suppressor properties of BRCA1 are generally thought to be linked to the gene's critical roles in the network of DNA damage response. In a recent report, BRCA1-mediated epigenetic repression at the promoter region of miRNA-155 was identified as a novel mechanism by which BRCA1 carries out its tumor suppressor functions.

Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994, 266: 66-71. 10.1126/science.7545954.CrossRefPubMed

Smith SA, Easton DF, Evans DG, Ponder BA: Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nat Genet. 1992, 2: 128-131. 10.1038/ng1092-128.CrossRefPubMed

Roy R, Chun J, Powell SN: BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2011, 12: 68-78.CrossRefPubMedPubMedCentral

Stefansson OA, Jonasson JG, Johannsson OT, Olafsdottir K, Steinarsdottir M, Valgeirsdottir S, Eyfjord JE: Genomic profiling of breast tumours in relation to BRCA abnormalities and phenotypes. Breast Cancer Res. 2009, 11: R47-10.1186/bcr2334.CrossRefPubMedPubMedCentral

Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED, Simpson JT, Stebbings LA, Leroy C, Edkins S, Mudie LJ, Greenman CD, Jia M, Latimer C, Teague JW, Lau KW, Burton J, Quail MA, Swerdlow H, Churcher C, Natrajan R, Sieuwerts AM, Martens JW, Silver DP, Langerod A, Russnes HE, Foekens JA, Reis-Filho JS, van 't Veer L, Richardson AL, Borresen-Dale AL, et al: Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature. 2009, 462: 1005-1010. 10.1038/nature08645.CrossRefPubMedPubMedCentral

Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 2011, 12: 861-874.CrossRefPubMed

Krutovskikh VA, Herceg Z: Oncogenic microRNAs (OncomiRs) as a new class of cancer biomarkers. Bioessays. 2010, 32: 894-904. 10.1002/bies.201000040.CrossRefPubMed

Lopez-Serra P, Esteller M: DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene. 2011, [Epub ahead of print]

Chang S, Wang RH, Akagi K, Kim KA, Martin BK, Cavallone L, Haines DC, Basik M, Mai P, Poggi E, Isaacs C, Looi LM, Mun KS, Greene MH, Byers SW, Teo SH, Deng CX, Sharan SK: Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155. Nat Med. 2011, 17: 1275-1282. 10.1038/nm.2459.CrossRefPubMedPubMedCentral

10.

Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS: Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009, 361: 123-134. 10.1056/NEJMoa0900212.CrossRefPubMed

11.

Ashworth A: A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol. 2008, 26: 3785-3790. 10.1200/JCO.2008.16.0812.CrossRefPubMed

12.

Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes IC, Repasky EA, Gabrielson E, Schutte M, Baylin SB, Herman JG: Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000, 92: 564-569. 10.1093/jnci/92.7.564.CrossRefPubMed

13.

Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE: Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006, 8: R38-10.1186/bcr1522.CrossRefPubMedPubMedCentral

14.

Futreal PA, Liu QY, Shattuckeidens D, Cochran C, Harshman K, Tavtigian S, Bennett LM, Haugenstrano A, Swensen J, Miki Y, Eddington K, Mcclure M, Frye C, Weaverfeldhaus J, Ding W, Gholami Z, Soderkvist P, Terry L, Jhanwar S, Berchuck A, Iglehart JD, Marks J, Ballinger DG, Barrett JC, Skolnick MH, Kamb A, Wiseman R: BRCA1 mutations in primary breast and ovarian carcinomas. Science. 1994, 266: 120-122. 10.1126/science.7939630.CrossRefPubMed

15.

Stefansson OA, Jonasson JG, Olafsdottir K, Hilmarsdottir H, Olafsdottir G, Esteller M, Johannsson OT, Eyfjord JE: CpG island hypermethylation of BRCA1 and loss of pRb as co-occurring events in basal/triple-negative breast cancer. Epigenetics. 2011, 6: 638-649. 10.4161/epi.6.5.15667.CrossRefPubMedPubMedCentral

16.

Veeck J, Ropero S, Setien F, Gonzalez-Suarez E, Osorio A, Benitez J, Herman JG, Esteller M: BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors. J Clin Oncol. 2010, 28: e563-e564. 10.1200/JCO.2010.30.1010.CrossRefPubMed

Title: BRCA1 as a tumor suppressor linked to the regulation of epigenetic states: keeping oncomiRs under control
Authors: Olafur Andri Stefansson
Manel Esteller
Publication date: 01-04-2012
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr3119

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2012

A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study

Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

Reproductive aging-associated common genetic variants and the risk of breast cancer

Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast cancer is associated with TP53mutation and poor clinical outcome

Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer

Advances in molecular imaging for breast cancer detection and characterization

Keynote webinar | Spotlight on antibody–drug conjugates in cancer