Mutational heterogeneity may be common in melanoma
Mutational heterogeneity was observed in almost 20% of melanoma tumors, according to a study.
“Mutational heterogeneity can contribute to therapeutic resistance in solid cancers,” Gregory A. Chang, MD, of The Ronald O. Perelman Department of Dermatology at New York University School of Medicine, NYU Langone Health, and colleagues wrote. “In melanoma, the frequencies of intertumoral and intratumoral heterogeneity are controversial.”
The researchers used a multiplatform analysis of mutated driver and non-passenger genes to compare mutational heterogeneity in paired primary and metastatic tumors from 60 patients and multiple metastatic tumors from 39 patients with unavailable primary tumors. In total, 271 tumors underwent analysis. SNaPshot assays, Sanger sequencing, mutation-specific PCR or droplet digital PCR were the methods used to determine the presence or absence of BRAFV600, NRASQ61, TERT–124C>T and TERT–146C>T mutations.
Results showed mutations of all three types, with 39% demonstrating BRAF, 21% showing NRAS and/or 78% with TERT.
TERT mutant discordant tumors were observed in 13 patients, with seven of these patients showing a single tumor that had both TERT–124C>T and TERT–146C>T mutations present at different allele frequencies, according to the findings.
In another patient, a primary tumor contained a BRAF mutation, but no evidence of such a mutation was observed in at least one metastasis. The researchers suggested that mutation in a primary tumor but not in a metastasis may be due to polyclonality.
The overall rate of mutational heterogeneity in 99 patients who underwent this analysis was 18%. At least two of the aforementioned methods were used to confirm heterogeneity in these patients.
“These results suggest that some primary melanomas may be composed of subclones with differing mutational profiles,” Chang and colleagues wrote. “Such heterogeneity may be relevant to treatment responses and survival outcomes.”