GRCh38 · COSMIC v94

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Whole genome sequencing of melanomas in adolescent and young adults reveals distinct mutation landscapes and the potential role of germline variants in disease susceptibility.
Paper ID
COSP45777
Authors
Wilmott JS, Johansson PA, Newell F, Waddell N, Ferguson P, Quek C, Patch AM, Nones K, Shang P, Pritchard AL, Kazakoff S, Holmes O, Leonard C, Wood S, Xu Q, Saw RPM, Spillane AJ, Stretch JR, Shannon KF, Kefford RF, Menzies AM, Long GV, Thompson JF, Pearson JV, Mann GJ, Hayward NK and Scolyer RA
Affiliation
Melanoma Institute Australia, The University of Sydney, NSW, Australia.
Journal
International journal of cancer, 2018
ISSN: 1097-0215
PMID: 30178487 (view at PubMed or Europe PMC)
Abstract
Cutaneous melanoma accounts for at least >10% of all cancers in adolescents and young adults (AYA, 15-30 years of age) in Western countries. To date, little is known about the correlations between germline variants and somatic mutations and mutation signatures in AYA melanoma patients that might explain why they have developed a cancer predominantly affecting those over 65 years of age. We performed genomic analysis of 50 AYA melanoma patients (onset 10-30 years, median 20); 25 underwent whole genome sequencing (WGS) of both tumour and germline DNA, exome data was retrieved from 12 TCGA AYA cases, and targeted DNA sequencing was conducted on 13 cases. The AYA cases were compared with WGS data from 121 adult cutaneous melanomas. Similar to mature adult cutaneous melanomas, AYA melanomas showed a high mutation burden and mutation signatures of ultraviolet radiation (UVR) damage. The frequencies of somatic mutations in BRAF (96%) and PTEN (36%) in the AYA WGS cohort were double the rates observed in adult melanomas (Q< 6.0x10<sup>-6</sup> and 0.028, respectively). Furthermore, AYA melanomas contained a higher proportion of non-UVR related mutation signatures than mature adult melanomas as a proportion of total mutation burden (P=2.0x10<sup>-4</sup> ). Interestingly, these non-UVR mutation signatures relate to APOBEC or mismatch repair pathways, and germline variants in related genes were observed in some of these cases. We conclude that AYA melanomas harbour some of the same molecular aberrations and mutagenic insults occurring in older adults, but in different proportions. Germline variants that may have conferred disease susceptibility correlated with somatic mutation signatures in a subset of AYA melanomas. This article is protected by copyright. All rights reserved.
Paper Status
Curated