To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed.,Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature.,Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1.,Mutations and amplification of KIT are also common.,Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common.,Complex rearrangements occur recurrently and are associated with amplification of TERT, CDK4, MDM2, CCND1, PAK1 and GAB2, indicating potential therapeutic options.,Acral melanoma occurs on the soles of the feet, palms of the hands and in nail beds.,Here, the authors reports the genomic landscape of 87 acral melanomas and find that some tumors harbor a UV signature and that the tumors are diverse at the levels of mutational signatures, structural aberrations and copy number signatures.
The detection of V600E BRAF mutation in melanoma is fundamental since here BRAF inhibitors represent an effective treatment.,Non-V600E BRAF mutations that may also respond are not detected by certain screening methods.,Thus, knowledge about detection of these mutations is needed.,A total of 276 tumour samples from 174 melanoma patients were investigated for BRAF mutations by pyrosequencing.,Rare mutations were confirmed by capillary sequencing and compared with findings from COBAS test and immunohistochemistry using a novel BRAF antibody.,Melanoma type, localisation, and survival were summarised.,BRAF mutations were found in 43% of patients (124 tumours in 75 patients).,Among those, 14 patients (18.7%) exhibited rare mutations.,The V600EK601del and V600DK601del mutations have never been described before in melanoma.,Furthermore, V600K, V600E2, and V600D, V600G, V600R, and L597S mutations were detected.,Mutations were not detected by COBAS test in 7 out of these 14 patients and immunohistochemistry only reliably detected patients with the V600E2 and V600EK601del mutation.,Accurate diagnosis of rare BRAF mutations is crucial.,We show that pyrosequencing is accurate, highly sensitive, reliable, and time saving to detect rare BRAF mutations.,Missing these rare variant mutations would exclude a subset of patients from available effective BRAF-targeting therapy.