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BRCA-2 and Breast Cancer

BRCA-2 and Breast Cancer. Natasha Adlakha Bio445. Discovery in Breast Cancer. Reverse Genetics BR east CA ncer Gene 2 -1995 Chromosome 13 Tumor suppressor gene Penetrance Familial, sporadic –different “2 hit”. www.cellsignal.com/products/9012.html. Normal Functions.

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BRCA-2 and Breast Cancer

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  1. BRCA-2 and Breast Cancer Natasha Adlakha Bio445

  2. Discovery in Breast Cancer • Reverse Genetics • BReast CAncer Gene 2 -1995 • Chromosome 13 • Tumor suppressor gene • Penetrance • Familial, sporadic –different “2 hit” www.cellsignal.com/products/9012.html

  3. Normal Functions • Aids in Homologous Recombination Pellegrini et al 2004

  4. Key points • BRCA2, RAD51 arrive at damaged site • Complex formation • Quandary of BRC4 • No BRCA2 protein leads to instability: • Breaks and aberrations • Repair by non-homologous end joining (below) Powell et al 2003 Powell et al 2003 Takeda et al 2001

  5. Mice Knockout leads to..? • -/- die early in development • Role of p53 • Limitations of mice –use Cre-lox • Results • BRCA-2 Paradox http://www2.mrc-lmb.cam.ac.uk/groups/kjp/research.html

  6. Future Research • Tissue specificity – why breast? • Gender bias • Humanized mouse models • Specific genotype-phenotype correlations • Paradox—secondary tumor suppressor gene mutations www.humurine.com/services.php

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