The prevalence of KRAS and BRAF mutation in colorectal cancer patients in Bali

Abstract

Mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog gene) and BRAF (v‐Raf murine sarcoma viral oncogene homolog B1) gene play a significant role in primary resistance to colorectal cancer therapy. Around 85‐90% of KRAS mutations in colorectal cancer occur in exon 2 (codon 12 and 13), whereas approximately 96% of BRAF mutations occur in exon 15 codon 600 (V600E). This study aimed to determine the prevalence and mutation characteristics of the KRAS and BRAF genes in colorectal cancer patients in Bali. The DNA was isolated from 44 formalin‐fixed paraffin‐embedded colorectal cancer samples which were stored in the Department of Pathology, Sanglah General Hospital in 2017. Detection of mutation was carried out by polymerase chain reaction (PCR) and direct sequencing. Out of 44 samples, only 27 were successfully amplified and sequenced. Our findings showed six samples (22.2%) with mutated KRAS at codons 12 and 13 (including two samples with G12D, one sample with G12V, and three samples with G13D). Interestingly, we found three samples (11.1%) of BRAF mutation, including two samples with V600E mutation and one with V600L mutation. Taken together, our results showed that KRAS and BRAF mutations were identified and occurred exclusively. Further studies are essential to identify the correlation of these mutations with colorectal cancer prognosis and response to chemotherapy

Identıfıcatıon of KRAS Mutatıons in Colorectal Carcınoma Patıents at Dr. M. Djamıl Hospıtal, West Sumatra-Indonesıa

“…The tumour was found in the cecum colon, descending colon, sigmoid colon, and rectum (Table 1). Previous research in Indonesia found that the incidence of colorectal cancer was higher in people over 50 (Indrayani M & Sriwidyani, 2017;Ni Nyoman et al, 2022;Saleh et al, 2019). Molenaar et al reported that 90% of CRC occurs at ages above 50.…”

“…In Bali, males were more likely to develop colorectal cancer, and the risk increased with age. KRAS mutations in exon two have been identified, with G13D being the most common, followed by G12D and G12V (Ni Nyoman et al, 2022). In West Java people, KRAS and p53 mutations are involved in carcinogenesis and have a significant association between KRAS gene expression and p53 immuno-expressions in colorectal adenocarcinoma KRAS (Rachmawati et al, 2019).…”

BRAF V600E Mutation in Ameloblastoma: A Systematic Review and Meta-Analysis

“…Even though the status and exact mechanisms are still unclear, a high prevalence status may indicate a new treatment area exploration concerning this specific mutation. Previously, the BRAF V600E mutation focused on malignant tumours, where the prevalence was approximately 74.6% for papillary thyroid carcinoma [ 95 ], 7.4% for colorectal cancer [ 96 ], and 60% for melanomas [ 97 ]. According to previous studies, several gene mutations have been identified in the background of BRAF V600E positive mutation in ameloblastoma, including somatic mutation in cyclin-dependent kinase inhibitor 2A ( CDKN2A ), catenin beta 1 ( CTNNB1 ), fibroblast growth factor receptors ( FGFR ), Kirsten rat sarcoma virus ( KRAS ), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ), and phosphatase and tensin homolog ( PTEN ) [ 19 , 98 ].…”

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…The CIMP, which is characterized by CG dinucleotide methylation in the promoters of numerous genes, is associated with distinct clinical and pathological attributes in tumors. These subtypes, as described by Jass Classification, include CIMP high/MSI high (12% of CRC), CIMP low/MSI low or microsatellite stable (20%), CIMP negative/microsatellite stable (57%), and Hereditary Non Polyposis Colorectal Cancer (HNPCC), with CIMP negative/MSI high and negative for BRAF mutations [7,[9][10][11][12]. Testing for MSI and MMR protein deficiency is commonly the first step in LS diagnostics due to germline mutations of MMR genes.…”