BRCA1and Breast

CancerMadeline Ryan

3/17/2015

The BRCA1 gene product is involved in homologous recombination

Homologous recombination is a repair mechanism for dsDNA breaks

BRCA1 pairs with Rad51 during the

strand invasion step

of HR

Mouse models and immunofluorescent microscopy helped us understand BRCA1

function

BRCA1 is a tumor suppressor

It must undergo loss of heterozygosity

(LOH)

Why breast cancer?

PARP inhibitors are in ongoing clinical trials for treatment of BRCA

gene positive patients

• ~8% of women will develop breast cancer

• 55-65% of women with an inherited BRCA1 mutation will develop breast cancer

• 5-10% of breast cancers in the U.S. are linked to an inherited mutation

• Women with the BRCA1 mutation tend to have triple-negative breast cancer

ReferencesRajan, J. V., Wang, M., Marquis, S. T., & Chodosh, L. A. (1996). Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 93(23), 13078–13083.

Venkitaraman, A. R. (2001). Functions of BRCA1 and BRCA2 in the biological response to DNA damage . Journal of Cell Science, 114, 3591-3598.

Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D. V., & Boehning, D. (2012). Structure-Function of the Tumor Suppressor BRCA1. Computational and Structural Biotechnology Journal, 1, e201204005. doi:10.5936/csbj.201204005

Evers, B., Jonkers, J. (2006). Mouse models of BRCA1 and BRCA2 deficiency: past lessons, current understanding and future prospects. Oncogene, 25, 5885-5897.

Scully, R., Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., Ashley,T., Livingston, D. M., (1997). Association of BRCA1 with Rad51 in Mitotic and Meiotic Cells. Cell, 88, 265-275.

Welsch, P., King, M. (2001) BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Human Molecular Genetics, 10, 705-713.

Ohta, T., Sato, K., Wu, W. (2011). The BRCA1 ubiquitin ligase and homologous recombination repair. FEBS Letters, 585, 2836-2844.

Maxwell, K., Domchek, S. (2012). Cancer treatment according to BRCA1 and BRCA2 mutations. Nat. Rev. Cllin. Oncol., 9, 520-528.

Photo References

http://www.multivu.com/players/English/7373551-us-fda-approves-first-in-class-lynparza-olaparib-treatment-women-brca-mutated-advanced-ovarian-cancer/

http://www.rxlist.com/lynparza-drug.htm

http://www.onclive.com/publications/Oncology-live/2012/July-2012/The-PARP-Inhibitors-Down-But-Not-Out

https://bioofcancer.wordpress.com

http://sherryimm.blogspot.com

http://ghr.nlm.nih.gov/gene/BRCA1

http://www.prweb.com/releases/2013/2/prweb10445267.htm

http://www.nationalbreastcancer.org/triple-negative-breast-cancer

http://www.uh.edu/news-events/tip-sheets/2014/10314BreastCancer.php