Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer

Anna Loginova, Yuri Shelygin, Vitaly Shubin, Sergey Achkasov, Alexey Ponomarenko,  Dmitry Shakhmatov, Sergey Skridlevskiy, Yuri Vaganov, Vladimir Kashnikov,  Alexey Tsukanov

Abstract:

Colorectal cancer (CRC) is one of the most common malignancies in the world. It’s estimated about 1.8 M new CRC cases worldwide per year. A somatic mutation in the BRAF gene in the tumor is a negative prognostic factor. This work is aimed at studying the clinical and genetic characteristics of Russian CRC patients with the BRAF mutation. The BRAF mutations were studied by Sanger sequencing and digital droplet PCR in 489 patients and found in 34 (7%) cases. The most common mutation was p.V600E (82%). Also, rare variants were found: p.K601E, p.N581I, p.G596R, and p.D594N. All the patients with rare mutations were characterized by an unfavorable prognosis of the disease. The clinical features of the patients with BRAF mutations in the study include the predominant primary tumor site in the rectum, in addition to the right colon. Then, most of the cases were diagnosed in the advanced stages of the disease and were represented by high-grade adenocarcinomas. This article demonstrates the feasibility of analysis of the entire exon 15 of BRAF gene in CRC patients regardless of tumor localization.