BRAF alterations are associated with complex mutational profiles in malignant melanoma

摘要: To evaluate the mutational profiles associated with BRAF mutations in human melanoma, we have studied BRAF, RAS, PTEN, TP53, CDKN2A and CDK4 genes their expression melanoma lesions. Owing to lack of sufficient material from fresh specimens, employed short-term cell lines obtained biopsies. In all, 41 eight primary lesions, 20 nodal, 11 cutaneous two visceral metastases patients sporadic (n=31), familial (n=4) multiple (n=2) were analysed. The results revealed novel missense genes. Overall, activating loss functional p16 ARF detected majority melanomas (29/41, 36/41 29/41, respectively), while PTEN alterations/loss, NRAS TP53 occurred less frequently (6/41, 6/41 10/41, respectively). resulting 12 profiles, p16/ARF mutated BRAFV599E was most represented (n=15). addition, always accompanied alterations, found association or absence activation. p16/ARFDelta+BRAF/RAS profile significantly a longer survival, complex highly aggressive disease poor survival. These data support existence several molecularly defined groups which likely reflect different clinical/biological behaviour, thus suggesting that more extensive molecular classification would impact its clinical management.