Abstract

BRAF mutation is one of the most common driver gene mutations in non-small cell lung cancer (NSCLC) patients, especially in adenocarcinoma. BRAF alterations have been identified with the clinical application of next generation sequencing (NGS),however, mutation profile and co-occurring genomic alterations of BRAF have not been fully understood in Chinese non-small cell lung cancer patients. We enrolled 14703 Chinese NSCLC patients with confirmed histology subtype of adenocarcinoma, squamous carcinoma and large cell carcinoma. FFPE samples and matched peripheral blood or plasma were sequenced for NGS based 1021 cancer genes panel assay. Comprehensive genomic profiling including single nucleotide variants (SNV), short and long insertion and deletion (Indel), copy number variations (CNV) and gene arrangement/fusion were analyzed. 1.78% (261/14703) of Chinese NSCLC patients harbored at least one BRAF genomic alteration, which was mainly composed of patient with SNVs and Indels (97.3%, 254 patients), copy number variations (16.1%, 42 patients), and gene rearrangements (5.0%, 13 patients). None BRAF CNV was detected. Of the 42 patients carried CNV, 38 of them carried both CNV and BRAF SNV/Indel, whereas two of them carried both CNV and gene arrangement/fusion and two of patients carried aforementioned three types of alteration. BRAF V600E were the most common BRAF mutations, which accounted for 36% of all BRAF mutation, respectively. The most common resistant alteration G469A accounted for 11%. A total of nine types of BRAF rearrangement were detected from eight patients. AGK-BRAF were the most common BRAF rearrangement, which accounted for 36% of all BRAF rearrangement. Further analysis of co-occurring BRAF mutations revealed that of BRAF mutated Chinese NSCLC patients harbored both BRAF mutations and other driver gene mutation, such as EGFR, KRAS, PI3KCA. This study revealed BRAF variation in approximately 1.78% of Chinese NSCLC patients. BRAF V600E were the most common BRAF mutations, which accounted for 36% of all BRAF mutation. BRAF mutated Chinese NSCLC patients harbored both BRAF mutations and other driver gene mutation, such as EGFR, KRAS, PI3KCA.

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