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

Jamal H. Carter, Li Hui Tseng, Gang Zheng, Jonathan Dudley, Peter Illei, Christopher D. Gocke, James R. Eshleman, Ming Tseh Lin

Research output: Contribution to journalArticle

27 Citations (Scopus)

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
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Mutation
Colorectal Neoplasms
Exons
Melanoma
Molecular Pathology
Gene Frequency
Codon
Lung Neoplasms
Neoplasms
Lymph Nodes
Alleles
Neoplasm Metastasis

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Non-p.V600E BRAF mutations are common using a more sensitive and broad detection tool. / Carter, Jamal H.; Tseng, Li Hui; Zheng, Gang; Dudley, Jonathan; Illei, Peter; Gocke, Christopher D.; Eshleman, James R.; Lin, Ming Tseh.

In: American Journal of Clinical Pathology, Vol. 144, No. 4, 01.01.2015, p. 620-628.

Research output: Contribution to journalArticle

Carter, JH, Tseng, LH, Zheng, G, Dudley, J, Illei, P, Gocke, CD, Eshleman, JR & Lin, MT 2015, 'Non-p.V600E BRAF mutations are common using a more sensitive and broad detection tool', American Journal of Clinical Pathology, vol. 144, no. 4, pp. 620-628. https://doi.org/10.1309/AJCP85ATMJOZOUDJ
Carter, Jamal H. ; Tseng, Li Hui ; Zheng, Gang ; Dudley, Jonathan ; Illei, Peter ; Gocke, Christopher D. ; Eshleman, James R. ; Lin, Ming Tseh. / Non-p.V600E BRAF mutations are common using a more sensitive and broad detection tool. In: American Journal of Clinical Pathology. 2015 ; Vol. 144, No. 4. pp. 620-628.
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