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.
Ipilimumab, an antibody that enhances T-cell activation, may augment immunogenicity of tumor cells that are injured by radiation therapy.,We hypothesized that patients with melanoma brain metastasis treated with both ipilimumab and radiotherapy would have improved overall survival, and that the sequence of treatments may affect disease control in the brain.,We analyzed the clinical and radiographic records of melanoma patients with brain metastases who were treated with whole brain radiation therapy or stereotactic radiosurgery between 2005 and 2012.,The hazard ratios for survival were estimated to assess outcomes as a function of ipilimumab use and radiation type.,Seventy patients were identified, 33 of whom received ipilimumab and 37 who did not.,The patients who received ipilimumab had a censored median survival of 18.3 months (95% confidence interval 8.1-25.5), compared with 5.3 months (95% confidence interval 4.0-7.6) for patients who did not receive ipilimumab.,Ipilimumab and stereotactic radiosurgery were each significant predictors of improved overall survival (hazard ratio = 0.43 and 0.45, with P = 0.005 and 0.008, respectively).,Four of 10 evaluable patients (40.0%) who received ipilimumab prior to radiotherapy demonstrated a partial response to radiotherapy, compared with two of 22 evaluable patients (9.1%) who did not receive ipilimumab.,Ipilimumab is associated with a significantly reduced risk of death in patients with melanoma brain metastases who underwent radiotherapy, and this finding supports the need for multimodality therapy to optimize patient outcomes.,Prospective studies are needed and are underway.