Next-generation sequencing increases actionable mutation detection in malignant melanoma

Source: Healio.com/hematology-oncology, April 2015

NEW YORK — The use of next-generation sequencing in multi-gene targeted panel testing identified a considerable number of actionable mutations among patients with malignant melanoma, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

Multi-gene panel testing through next-generation sequencing has become a valuable strategy to identify actionable mutations and yield prognostic information in patients with molecular melanoma. Due to the increasing number of approved therapies that target specific pathways, next-generation sequencing may help identify ideal treatments, according to study background.

Matthew Zibelman, MD, a fellow at Fox Chase Cancer Center in Philadelphia, and colleagues evaluated archived tumor samples from 60 patients with high-risk and recurrent malignant melanoma to identify mutations in targeted regions of 50 cancer-related genes. The investigators summarized mutational profiles for all samples, then correlated them with various clinicopathologic features.

Median patient age was 71 years (range, 28-90) and about two-thirds (66.7%) were men.

Zibelman and colleagues identified 101 mutations that affected 25 unique genes.

The most commonly identified genetic mutations were NRAS (33.3%), BRAF (30%), p53 (23.3%) and CDKN2A (11.7%). The majority of BRAF mutations (88.9%) were BRAFV600.

Researchers determined more than two-thirds of patients (68.3%) had mutations (NRAS, BRAF and KIT) that were potentially actionable with commercially available drugs, and 21 of the other mutations identified could be targetable on a clinical trial, the researchers wrote.

Twenty-six patients (43.3%) had two or more genetic alterations, whereas only eight (13.3%) had no identifiable mutations. Seven of the eight patients with no identifiable mutation had acral or mucosal malignant melanoma.

“Multi-gene targeted panel testing by next-generation sequencing reveals a significant number of actionable mutations in patients with malignant melanoma,” Zibelman and colleagues wrote. “Patients with non-cutaneous malignant melanoma were less likely to have identifiable mutations.” – by Cameron Kelsall

Reference:

Zibelman M, et al. Molecular markers in malignant melanoma: Experience at an NCI-designated cancer center. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.