Next-Generation Sequencing Adds Value by Detecting More Mutations Than Polymerase Chain Reaction in Melanoma

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Since next-generation sequencing reflex testing has been implemented, several cases of potentially actionable mutations have been identified that would not have been caught by PCR alone.
Since next-generation sequencing reflex testing has been implemented, several cases of potentially actionable mutations have been identified that would not have been caught by PCR alone.

Targeted next-generation sequencing (NGS) to detect BRAF mutations provided more information and identified more potentially actionable mutations than allele-specific polymerase chain reaction (PCR) in samples from patients with advanced metastatic melanoma, according to a study published in Virchows Archive.1

Molecular characterization of metastatic melanoma is a critical component of appropriate treatment selection. “BRAF V600K is a biomarker for several [U.S. Food and Drug Administration (FDA)] therapies. Recent reports suggest that patients with advanced melanomas with BRAF non-V600E/K mutations may benefit from anti-BRAF/anti-MEK therapies,” Navid Sadri, MD, PhD, of Case Western Reserve University School of Medicine in Cleveland, Ohio, and an author of the study, told Cancer Therapy Advisor.

A BRAF mutation is present in up to 50% of metastatic melanoma cases, with the most common resulting in a valine to glutamic acid (approximately 80%) or a valine to lysine (approximately 10%) change at codon 600. Metastatic melanoma can also be associated with mutations in other genes, such as NRAS or KIT.

Prior to the introduction of NGS, allele-specific PCR was used to detect specific mutations, such as BRAF mutations that result in the V600E or V600K variants. Allele-specific PCR uses oligonucleotide primers of known genotypes to detect single nucleotide changes in DNA of an unknown genotype. This technique is limited to detecting specific mutations, Dr Sadri noted, and other traditional sequencing techniques, such as Sanger sequencing, have low sensitivity.

NGS, in contrast, is an ultra high–throughput technology that uses a library to conduct parallel sequencing of millions of DNA fragments. “The advantage of NGS is that it is not specific for a certain mutation; therefore, any change in the sequence may be identified with relatively high sensitivity,” Dr Sadri said.

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