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

Natasa Broit, Peter A Johansson, Chloe B Rodgers, Sebastian T. Walpole, Felicity Newell, Nicholas K. Hayward, Antonia L Pritchard

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18 Citations (Scopus)
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Mucosal melanoma is a rare sub-type 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 (n = 173; fresh-frozen samples), 'validation' cohort (n = 48; formalin-fixed, paraffin embedded samples) and a second 'validation' cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in BRAF, KIT and NRAS were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed KIT, NF1, BRAF, NRAS, SF3B1 and SPRED1 as significantly mutated genes. ATRX and SF3B1 mutations occurred more commonly in lower anatomy melanomas, and CTNNB1 in the upper anatomy. NF1, PTEN, CDKN2A, SPRED1, ATM, CHEK2 and ARID1B were commonly affected by chromosomal copy loss, while TERT, KIT, BRAF, YAP1, CDK4, CCND1, GAB2, MDM2, SKP2 and MITF 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. Implications: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways.
Original languageEnglish
JournalMolecular Cancer Research
Early online date11 Mar 2021
Publication statusE-pub ahead of print - 11 Mar 2021


  • Mucosal melanoma
  • genomics
  • systematic review
  • meta-analysis


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