Human Genes Differ by Their UV Sensitivity Estimated Through Analysis of UV-Induced Silent Mutations in Melanoma

Authors

Ivan P Gorlov
Christopher I Amos
Spiridon Tsavachidis
Colin Begg
Eva Hernando
Chao Cheng
Ronglai Shen
Irene Orlow
Li Luo
Marc S Ernstoff
Joel Parker
Nancy E Thomas
Olga Y Gorlova
Marianne Berwick

Publication Date

10-1-2020

Journal

Human Mutation

DOI

10.1002/humu.24078

PMID

32643855

PMCID

PMC7794094

PubMedCentral® Posted Date

10-1-2021

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Genome, Human, Humans, Melanoma, Mutation, Oncogenes, Silent Mutation, Skin Neoplasms, Ultraviolet Rays, UV exposure, mutation rate, melanoma, COSMIC, CDKN2A

Abstract

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top five most UV-sensitive genes in the human genome. Melanoma driver genes have a higher UV-sensitivity compared with other genes in the human genome. The difference was more prominent for tumor suppressors compared with oncogene. The results of this study suggest that differential sensitivity of human transcripts to UV light may explain melanoma specificity of some driver genes. Practical significance of the study relates to the fact that differences in UV sensitivity among human genes need to be taken into consideration whereas predicting melanoma-associated genes by the number of somatic mutations detected in a given gene.

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