Non-p.V600E BRAF mutations are common using a more sensitive and broad detection tool

Jamal Carter, Li Hui Tseng, Gang Zheng, Jonathan Dudley, Peter B Illei, Christopher Gocke, James Eshleman, Ming-Tseh Lin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)620-628
Number of pages9
JournalAmerican Journal of Clinical Pathology
Volume144
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

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Keywords

  • BRAF
  • Colorectal cancer
  • Lung cancer
  • Melanoma
  • Next-generation sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

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