BRAF/NRAS Wild-Type Melanomas Have a High Mutation Load Correlating with Histologic and Molecular Signatures of UV Damage

摘要: Purpose: The mutation load in melanoma is generally high compared with other tumor types due to extensive UV damage. Translation of exome sequencing data into clinically relevant information therefore challenging. This study sought characterize mutations identified primary cutaneous melanomas and correlate these clinicopathologic features. Experimental Design: DNA was extracted from 34 fresh-frozen matched peripheral blood. Tumor histopathology reviewed by two dermatopathologists. Exome conducted rates were correlated age, sex, site, histopathologic variables. Differences between categories solar elastosis, pigmentation, BRAF / NRAS mutational status investigated. Results: average rate 12 per megabase, similar published results metastases. severely sun damaged (SSD) skin 21 Mb 3.8 non-SSD ( P = 0.001). BRAF/NRAS wild-type (WT) tumors had a higher –mutant (27 vs. 5.6 Mb; 0.0001). Tandem CC>TT/GG>AA comprised 70% all dinucleotide substitutions more common arising SSD 0.0008) WT 0.0007). Targetable potentially targetable tumors, including NF1 , KIT NOTCH1 spread over various signaling pathways. Conclusion: Melanomas have loads contain spectrum molecular subtypes - -mutant indicating multigene screening approaches combination therapies may be required for management patients. Clin Cancer Res; 19(17); 4589–98. ©2013 AACR .