Molecular evidence that cutaneous melanomas arise through multiple causal pathways

Cancer Science & Therapy

ISSN: 1948-5956

Open Access

Molecular evidence that cutaneous melanomas arise through multiple causal pathways

Global Summit on Melanoma & Carcinoma

July 14-15, 2016 Brisbane, Australia

Elke Hacker, Catherine Olsen, Marina Kvaskoff, Nirmala Pandeya, Abrey Yeo, Adele Green, Richard Williamson, Joe Triscott, Dominic Wood, Rohan Mortimore, Nick Hayward and David Whiteman

QIMR Berghofer Medical Research Institute, Australia
Sullivan Nicolaides Pathology, Australia
IQ Pathology, Australia
Queensland Medical Laboratory, Australia
Queensland University of Technology, Australia

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

There is increasing epidemiologic and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the pathway model for melanoma. Melanomas collected from 414 Australian patients were analyzed for MC1R status and twenty-five common mutations using the MelaCarta Panel designed by Agena Bioscience. Detailed phenotypic and sun exposure data were systematically collected from all patients. Mutually exclusive BRAF-mutant and NRASmutant tumors occurred at frequencies of 39% and 9% respectively. There was no association between germline MC1R variants and somatic BRAF mutations in melanomas from this population. However, we did observe differences within BRAF-mutant melanoma, with BRAFV600E mutations associated with increasing nevus counts, contiguous neval remnants and a family history of melanoma while there was an inverse association between the numbers of solar keratoses and excised skin cancers and BRAF V600E mutational status. Older patients were more likely to have melanomas harboring BRAF V600K or NRAS mutations and cumulative sun exposure showed an interesting trend, with highest risks of BRAF V600E and V600K mutations associated with the middle categories of sun exposure, suggestive of an intermittent pattern of sun exposure. This study demonstrates marked differences in the associations between sun exposure, melanocyte susceptibility and host characteristics with a suite of melanoma mutations, strongly suggestive of different casual pathways to melanoma development.

Biography :


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