A fundamental abnormality in cancer is the unchecked proliferation of cells. Rather than responding appropriately to signals that control normal cell division, cancer cells grow and divide in an uncontrolled manner, invade normal tissues and organs, and eventually spread throughout the body. We have shown that PARK2 is a critical regulator of the core cell cycle machinery that controls cell proliferation. PARK2, a gene on chromosome 6q25.2-q27 originally discovered as a frequent cause of autosomal recessive juvenile par-kinsonism (ARJP), has previously been identified as a tumor suppressor gene by our lab. Recently, through genetic analysis of approximately 5,000 tumors samples across 11 tumor types, we found that PARK2 undergoes copy number loss in about 30% of tumors, with deletions occurring most often in serous ovarian, breast, colon, and bladder carcinomas. Intriguingly, PARK2 genetic loss was mutually exclusive with amplification of the genes encoding cyclin D1 (CCND1), cyclin El (CCNE1), and CDK4, suggesting that PARK2 and these cell cycle machinery components interact in a common pathway. Aside from these results, our study dramatically demonstrates the power of in silico pan-cancer genetic analysis for elucidating novel biology.
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