Download BRCA1

BRCA1
and Breast
Cancer
Madeline 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
References
Rajan, 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, 705713.
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-brcamutated-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