Data from Meta-Analysis and Systematic Review of the Genomics of Mucosal Melanoma

Abstract

<div>Abstract<p>Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified. Datasets from these studies were collated to summarize mutations, structural variants, and regions of copy-number alteration. Studies using next-generation sequencing were divided into the “main” cohort (<i>n</i> = 173; fresh-frozen samples), “validation” cohort (<i>n</i> = 48; formalin-fixed, paraffin-embedded samples) and a second “validation” cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in <i>BRAF, KIT</i>, and <i>NRAS</i> were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed <i>KIT, NF1, BRAF, NRAS, SF3B1</i>, and <i>SPRED1</i> as significantly mutated genes. <i>ATRX</i> and <i>SF3B1</i> mutations occurred more commonly in lower anatomy melanomas and <i>CTNNB1</i> in the upper anatomy. <i>NF1, PTEN, CDKN2A, SPRED1, ATM, CHEK2</i>, and <i>ARID1B</i> were commonly affected by chromosomal copy loss, while <i>TERT, KIT, BRAF, YAP1, CDK4, CCND1, GAB2, MDM2, SKP2</i>, and <i>MITF</i> were commonly amplified. Further notable genomic alterations occurring at lower frequencies indicated commonality of signaling networks in tumorigenesis, including MAPK, PI3K, Notch, Wnt/β-catenin, cell cycle, DNA repair, and telomere maintenance pathways. This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted.</p>Implications:<p>Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways.</p></div>