What are the molecular pathways in melanoma?

Major molecular pathways that have been implicated in melanoma include p16 (25% to 50%) and p14^ARF (25% to 50%), microphthalmia-associated transcription factor (MITF) (50% to 75%), B-Raf (50% to 60%), and PTEN (15% to 25%). Furthermore, the antiapoptotic factor Bcl-2 is often overexpressed in melanoma. It should be stressed, that as noted above, not all melanomas are the same. In this regard, those melanomas that develop in younger patients on intermittently sun-exposed skin demonstrate a greater percentage of B-Raf mutations (>60%) than those melanomas that develop on chronically sun-exposed skin in older patients (<15%). In contrast, those melanomas that develop on chronically sun-exposed skin in older patients demonstrate a greater percentage of N-Ras mutations (20% to 40%). Along the same lines, melanomas that develop on acral and mucosal sites more demonstrate a greater percentage of c-Kit mutations (~40%) compared to non–sun-exposed (0%) and sun-exposed (30%) melanomas. Further, acral and mucosal melanomas demonstrate a lower percentage of B-Raf mutations (~20% and ~10%, respectively).


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