Non-p.V600E BRAF mutations are common using a more sensitive and broad detection tool
Journal
American Journal of Clinical Pathology
Journal Volume
144
Journal Issue
4
Pages
620-628
Date Issued
2015
Author(s)
Abstract
Objectives: To assess the performance of a next-generation sequencing (NGS) platform for the clinical detection of BRAF mutations. Methods: In this retrospective quality assessment of an NGS assay, we analyzed BRAF mutations within parts of exons 11 and 15 in 835 neoplastic tissues submitted to our molecular diagnostics laboratory. Results: The NGS assays detected a BRAF mutation in 5.9% of lung adenocarcinomas, 13% of colorectal cancers, and 44% of melanomas. Mutant allele frequencies were less than 20% in 28% of 88 BRAF-mutated specimens. Two lymph node specimens with subcapsular or infiltrative metastasis showed 1% to 2% mutant alleles. There were 26 unique BRAF mutations in exons 11 and 15, including three novel mutations. Mutations were located outside codon 600 in 39% of BRAF-mutated tumors. Lung adenocarcinomas showed significantly higher non-p.V600E mutations (86%) than did colorectal cancers (23%) and melanomas (34%). The three most common BRAF mutations in lung cancers accounted for only 41% of the observed BRAF mutations (p.D594G [18%], p.V600E [14%], and p.G469A [9%]). Conclusions: The NGS assay demonstrated a high analytic sensitivity and a broad reportable range for clinical detection of BRAF mutations. Elucidating the spectrum of non-p. V600E BRAF mutations in different malignancies is a first step toward understanding their clinical significance. ? American Society for Clinical Pathology.
Subjects
BRAF; Colorectal cancer; Lung cancer; Melanoma; Next-generation sequencing
SDGs
Other Subjects
B Raf kinase; B Raf kinase; BRAF protein, human; Article; codon; colorectal cancer; controlled study; exon; gene frequency; gene mutation; human; human tissue; limit of detection; lung adenocarcinoma; melanoma; metastasis; next generation sequencing; priority journal; pyrosequencing; quality control; retrospective study; sensitivity analysis; DNA microarray; DNA sequence; genetics; high throughput sequencing; neoplasm; nucleotide sequence; procedures; sensitivity and specificity; DNA Mutational Analysis; High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins B-raf; Retrospective Studies; Sensitivity and Specificity; Sequence Analysis, DNA
Publisher
American Society of Clinical Pathologists
Type
journal article