6 research outputs found
High concordance of BRAF mutational status in matched primary and metastatic melanoma
Background: Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumours. There is uncertainty regarding the frequency with which BRAF status differs between primary and metastatic sites. Methods: Between 2011 and 2016, 219 melanoma cases underwent BRAF testing in our institution. In 53 of these, paired primary and metastatic specimens were available for PCR and immunohistochemical evaluation. Results: 52 out of 53 cases (98%) showed concordant BRAF status between primary and metastatic site by IHC. In one case, a metastasis and its matched primary were positive by IHC but the metastasis was negative on PCR. On further investigation, PCR was positive in the primary and repeat PCR in the metastasis was positive, following macrodissection. Conclusions: Our results suggest that discordance of BRAF mutational status between primaries and metastases is a rare occurrence. In one case, immunohistochemistry provided strong evidence that initial PCR testing had provided a false negative result due to low tumour volume. Thus, in cases where tissue is difficult to obtain from a metastasis or unavailable, the primary tumour can be used with confidence
BRAF V600 mutation detection in melanoma: a comparison of two laboratory testing methods
High-throughput oncogene mutation profiling shows demographic differences in BRAF mutation rates among melanoma patients
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(V600E) 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(V600E)-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(V600E). Together, our data show that melanoma-driving mutations vary by demographic area, which has important implications for the clinical management of this disease