title: Gender Disparity and Mutation Burden in Metastatic Melanoma.
abstract: Gender differences in melanoma incidence and outcome have been consistently observed but remain biologically unexplained. We hypothesized that tumors are genetically distinct between men and women and analyzed the mutation spectra in 266 metastatic melanomas (102 women and 164 men) from The Cancer Genome Atlas (TCGA). We found a statistically significantly greater burden of missense mutations among men (male median 298 vs female median = 211.5; male-to-female ratio [M:F] = 1.85, 95% confidence interval [CI] = 1.44 to 2.39). We validated these initial findings using available data from a separate melanoma exome cohort (n = 95) and found a similar increase in missense mutations among men (male median 393 vs female median 259; M:F = 1.59, 95% CI = 1.12 to 2.27). In addition, we found improved survival with increasing log-transformed missense mutation count (univariate hazard ratio = 0.82, 95% CI = 0.69 to 0.98) for TCGA samples. Our analyses demonstrate for the first time a gender difference in mutation burden in cutaneous melanoma.
authors: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (SG, HT); Analytic and Translational Genetic Unit, Massachusetts General Hospital, Boston, MA (MA, MD); Broad Institute, Cambridge, MA (MA, MD); Chemistry and Chemical Biology Department, Harvard University, Cambridge, MA (MA); School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong (WG).
authors: Sameer
authors: S
authors: Gupta
authors: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (SG, HT); Analytic and Translational Genetic Unit, Massachusetts General Hospital, Boston, MA (MA, MD); Broad Institute, Cambridge, MA (MA, MD); Chemistry and Chemical Biology Department, Harvard University, Cambridge, MA (MA); School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong (WG).
authors: Mykyta
authors: M
authors: Artomov
authors: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (SG, HT); Analytic and Translational Genetic Unit, Massachusetts General Hospital, Boston, MA (MA, MD); Broad Institute, Cambridge, MA (MA, MD); Chemistry and Chemical Biology Department, Harvard University, Cambridge, MA (MA); School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong (WG).
authors: William
authors: W
authors: Goggins
authors: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (SG, HT); Analytic and Translational Genetic Unit, Massachusetts General Hospital, Boston, MA (MA, MD); Broad Institute, Cambridge, MA (MA, MD); Chemistry and Chemical Biology Department, Harvard University, Cambridge, MA (MA); School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong (WG).
authors: Mark
authors: M
authors: Daly
authors: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (SG, HT); Analytic and Translational Genetic Unit, Massachusetts General Hospital, Boston, MA (MA, MD); Broad Institute, Cambridge, MA (MA, MD); Chemistry and Chemical Biology Department, Harvard University, Cambridge, MA (MA); School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong (WG). htsao@partners.org.
authors: Hensin
authors: H
authors: Tsao
mesh_terms: D000328:Adult; D000368:Aged; D059472:Exome; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D016017:Odds Ratio; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015203:Reproducibility of Results; D017678:Sex Distribution; D012737:Sex Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D000096142:Cutaneous Malignant Melanoma
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human