Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations

Oncotarget
William BrunoPaola Ghiorzo

Abstract

Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/or immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized for germline status, and to investigate an interplay between germline and somatic variants. BRAF mutations were present in 68% of cases, while CDKN2A germline mutations were found in 16 % and p16 loss in tissue was found in 63%. TERT promoter somatic mutations were detected in 38% of cases while the TERT -245T>C polymorphism was found in 51% of cases. NRAS mutations were found in 39% of BRAF negative or undetermined cases. NF1 was expressed in all cases analysed. MC1R variations were both considered as a dichotomous variable or scored. While a positive, although not significant association between CDKN2A germline mutations, but not MC1R variants, and BRAF somatic mutation was found, we did not observe other associations between germline and somatic events....Continue Reading

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Citations

Mar 24, 2020·Journal of Cutaneous Pathology·Kiran MotaparthiPatrick O Emanuel
Mar 4, 2020·Expert Review of Molecular Diagnostics·Bruna Dalmasso, Paola Ghiorzo
Aug 7, 2021·Genes·Michele ManganelliGabriella Guida

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Methods Mentioned

BETA
PCR

Software Mentioned

R
SIFT taster
Phen
Poly
R Core Team
R Foundation for Statistical Computing
Mut

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