BRCA2 and melanoma: Examples of driver genes that are altered in multiple cancer types but have a tissue-specific functional impact include BRCA1/BRCA2, which are impacted by germ-line mutation but lead to cancer primarily in estrogen-sensitive tissues (e.g., breast and ovaries) [9], and BRAF, which can be effectively inhibited in BRAF-mutated melanoma but not in BRAF-mutated colon cancer [10].