Abstract
Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.
Highlights
Somatic mutations caused by various insults during life-time are one of the most important factors driving normal cells out of control and to become cancer cells
Immunohistochemistry was successfully performed for the 194 samples, and the BRAF V600E-specific antibody stained positively only on the two BRAF V600E-mutated samples, one with moderate intensity and the other with weak focal staining (Fig. 2). These results indicated that BRAF V600E specific antibody and the established real-time quantitative PCR (RT-qPCR) assay had a high concordance in BRAF V600E detection of lung cancer
The present results agree with earlier findings from other regions and countries, showing low incidence of the BRAF V600E mutation that tends to exist in adenocarcinoma
Summary
Somatic mutations caused by various insults during life-time are one of the most important factors driving normal cells out of control and to become cancer cells. Administration of BRAF inhibitors, such as vemurafenib and dabrafenib, have shown to improve the response and survival of patients with BRAF V600E mutations regardless of their previous treatment These inhibitors bring no significant benefit for patients with most of the other BRAF mutations, except those occurring at the 6 00th amino acid of BRAF, such as the other frequently observed V600K mutation (GTG > AAG), which are able to constitutively activate BRAF kinase activity both in monomeric or dimeric forms[10,11]. Despite these improvements, rapid progression and development of secondary skin cancers are frequently observed among patients with these monotherapies. Screening the BRAF V600E/K mutation with these two methods simultaneously could help improve detection accuracy
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