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 language | English (US) |
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Pages (from-to) | 620-628 |
Number of pages | 9 |
Journal | American journal of clinical pathology |
Volume | 144 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2015 |
Externally published | Yes |
Keywords
- BRAF
- Colorectal cancer
- Lung cancer
- Melanoma
- Next-generation sequencing
ASJC Scopus subject areas
- Pathology and Forensic Medicine