File(s) not publicly available

Presence and prevalence of UV related genetic mutations in uveal melanoma: Similarities with cutaneous melanoma

journal contribution
posted on 21.10.2020, 00:00 by AY Goh, Charmaine Ramlogan-SteelCharmaine Ramlogan-Steel, KS Jenkins, Jason SteelJason Steel, Christopher LaytonChristopher Layton
Ultraviolet (UV) radiation is an accepted etiological factor in cutaneous melanoma (CM), however its role in Uveal Melanoma (UM) is controversial. Partly as a consequence, CM and UM are often considered to be separate conditions, and advances in the treatment of CM have not led to joint clinical trials or parallel improvements in survival of UM. This study hypothesized that a subset of UM tumors display evidence of genetic changes consistent with UV-related damage similar to that shown in CM. Analysis of the Broad Institute's Firebrowse depository of 80 UM samples and 343 CM samples, together with the Sanger Institute's Catalogue of Somatic Mutations in Cancer depository of 995 UM and 12,447 CM samples was undertaken to identify the most frequently mutated genes, mutation types and specific nucleotide variants (SNVs) in each condition. Somatic mutation data was cross-correlated and shared mutations assessed against known effects of UV radiation. The proportion of samples with C>T substitutions (a classic genetic marker of UV-related damage) was higher in UM than CM on both DNA strands (17.0% vs 13.1% , p = 0.038). The most frequently encountered cross-correlated mutated genes between UM and CM were, in order, BRAF, NRAS, TP53, CDKN2A, TERT, PTEN, ARID2 and KMT2C, with multiple common BRAF point mutations. Each cross-correlated mutation, and each common point mutation in BRAF, was associated with UV-related mechanistic changes. These findings support the hypothesis that the etiology of a substantial minority of UMs may be more UV dependent than previously recognized.

History

Volume

67

Issue

5

Start Page

958

End Page

971

Number of Pages

14

eISSN

1338-4317

ISSN

0028-2685

Location

Slovakia

Publisher

Vydavatel'stvo Slovenkej Akademie Vied/Veda Publishing House of the Slovak Academy of Sciences

Language

eng

Peer Reviewed

Yes

Open Access

No

Acceptance Date

02/10/2019

Era Eligible

Yes

Journal

Neoplasma

Usage metrics

Categories

Exports