Journal Article


William M Gallagher
Bryan T Hennessy
John P Crown
Paul P Donnellan
Zsolt Orosz
Allan O'Keeffe
Clodagh M McDermott
Padraic J Regan
Derek G Power
Ruben Yela
and 19 others



high throughput demographic profiling oncogene patients single nucleotide melanoma mutation

High-throughput oncogene mutation profiling shows demographic differences in BRAF mutation rates among melanoma patients. (2015)

Abstract Because of advances in targeted therapies, the clinical evaluation of cutaneous melanoma is increasingly based on a combination of traditional histopathology and molecular pathology. Therefore, it is necessary to expand our knowledge of the molecular events that accompany the development and progression of melanoma to optimize clinical management. The central objective of this study was to increase our knowledge of the mutational events that complement melanoma progression. High-throughput genotyping was adapted to query 159 known single nucleotide mutations in 33 cancer-related genes across two melanoma cohorts from Ireland (n=94) and Belgium (n=60). Results were correlated with various clinicopathological characteristics. A total of 23 mutations in 12 genes were identified, that is - BRAF, NRAS, MET, PHLPP2, PIK3R1, IDH1, KIT, STK11, CTNNB1, JAK2, ALK, and GNAS. Unexpectedly, we discovered significant differences in BRAF, MET, and PIK3R1 mutations between the cohorts. That is, cases from Ireland showed significantly lower (P<0.001) BRAF mutation rates (19%) compared with the mutation frequency observed in Belgian patients (43%). Moreover, MET mutations were detected in 12% of Irish cases, whereas none of the Belgian patients harbored these mutations, and Irish patients significantly more often (P=0.027) had PIK3R1-mutant (33%) melanoma versus 17% of Belgian cases. The low incidence of BRAF-mutant melanoma among Irish patients was confirmed in five independent Irish cohorts, and in total, only 165 of 689 (24%) Irish cases carried mutant BRAF. Together, our data show that melanoma-driving mutations vary by demographic area, which has important implications for the clinical management of this disease.
Collections Ireland -> National University of Ireland Galway -> PubMed

Full list of authors on original publication

William M Gallagher, Bryan T Hennessy, John P Crown, Paul P Donnellan, Zsolt Orosz, Allan O'Keeffe, Clodagh M McDermott, Padraic J Regan, Derek G Power, Ruben Yela and 19 others

Experts in our system

William M Gallagher
University College Dublin
Total Publications: 148
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33
John Crown
Dublin City University
Total Publications: 104