Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan

Abstract

Background: RAS/BRAF V600E mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant metastatic CRC (mCRC) in Japan.Methods: Chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAFV600E status was investigated. RAS/BRAFV600E status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method.Results: RAS/BRAF V600E mutations were detected in 54% of cases (KRAS codon 12 = 26%; KRAS codon 13 = 11%; minor RAS [non-KRAS codon 12 and non-KRAS codon 13] = 10%; and BRAFV600E = 7%). BRAFV600E-mutant CRC mainly existed in the right colon, whereas minor RAS-mutant CRC was predominantly present in the left colon. Minor RAS-mutant CRC was associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR] = 2.45; 95% confidence interval [CI] = 0.92–6.57; p = 0.073) and significantly shorter overall survival than major RAS-mutant CRC (HR = 4.77; 95% CI = 1.44–15.77; p = 0.010). The KRAS codon 12 mutant group showed significantly longer overall survival than the minor RAS mutant groups (HR = 0.06; 95% CI = 0.01–0.47; p < 0.00) and had extended progression-free survival compared with the codon 13 group.Conclusions: In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant mCRC in Japan.

A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population

“…The frequency of BRAF mutation varies globally, approximately 1.1-25% [16,49,[135][136][137][138][139]. The prevalence of BRAF mutation obtained in this study was 5.6% (95% CI: 3.9-8.0), and this is conforming 14 BioMed Research International with the several existing findings, i.e., 1.1 to 5.8% in Asian studies and 5-21% in western studies [112,131,134,[140][141][142]. Another reason for these prevalence similarities could be associated with genetic homogeneity as the studies involve certain regions, and their lifestyles and diet are almost similar [143].…”

“…BRAF is also a member of the RAF gene subfamily that, like KRAS, performs its function in the EGFR downstream cascade, but their mutations are less frequent than the KRAS gene mutations. Among the BRAF gene, BRAFV600E mutation is the most prevailing [134], and in this present study, BRAFV600E mutation is used to examine the prevalence of BRAF gene mutation in CRC. The frequency of BRAF mutation varies globally, approximately 1.1-25% [16,49,[135][136][137][138][139].…”

Single-organ Pulmonary Metastasis is a favorable prognostic factor in Metastatic Colorectal Cancer Patients Treated with FOLFIRI and Vascular Endothelial Growth Factor Inhibitors

“…Giannou et al showed that NRAS mutations promote colonization of the lungs by various tumor types in mouse models [31]. However, Ikoma et al investigated the prognostic features of patients with RAS mutant CRC in Japan and showed that NRAS mutant CRC tended to have a short OS [32]. The number of NRAS-mutated CRC cases was small in our cohort, and our ndings require replication in larger investigations.…”

Case report: administration of immune checkpoint inhibitor for SMARCB1 (INI1)-negative rhabdoid carcinoma with microsatellite instability (MSI)-high in the right colon

“…MSI-high status is characterized by a frequent right-sided colon location, poorly differentiated histology, signet ring cell carcinoma or mucinous carcinoma component, and numerous infiltrating lymphocytes [15]. BRAF V600E mutation is also frequently noted in right-sided colon cancer, and patients with tumors with MSI-high status more commonly have this mutation [16]. Loss of MLH1 or MSH6 was also noted in SMARCB1-negative rhabdoid carcinoma of the colon (Table 1), and the present patient showed an MSIhigh phenotype.…”