KRAS/NRAS/BRAF Mutation Rate in Saudi Academic Hospital Patients With Colorectal Cancer

Abstract

Background: KRAS/NRAS/BRAF mutations are prognostic and predictive molecular biomarkers for colorectal cancers (CRCs). CRC has different frequencies in the population for mutations such as KRAS , NRAS , and BRAF . The aim of this study is to verify the frequency of the somatic KRAS/NRAS/BRAF mutations in Saudi academic hospital patients diagnosed with CRC and compare it with those estimated at the local and national levels. Methods: Out of 280 colorectal carcinomas diagnosed between 2018 and 2021 (primary and secondary), 97 (34.6%) were evaluated by Next Generation Sequencing (NGS) for colorectal cancer molecular markers. Four of these failed the PCR amplification, while 93 were successfully tested. KRAS , NRAS, and BRAF mutation rates and clinical pathological characteristics were recorded. Results: In this retrospective study, almost half of the tested samples were reported to have a clinically significant mutation (46/93 positive calls, while others were triple-negative). We found that the most prevalent mutation in KRAS (45.2%) was followed by NRAS (2.2%) and BRAF (2.2%). KRAS p.G12D accounted for the most frequently resulting variant (17/42, 40.5%). Second in ranking is KRAS p. G12V (6/42, 14.3%). Conclusion: This study is the first to describe the frequency of triple mutations in the city of Jeddah. The findings are consistent with previous research conducted in the Middle East and other local Saudi centers.

RAS/RAF/MAPK Pathway Mutations as Predictive Biomarkers in Middle Eastern Colorectal Cancer: A Systematic Review

“…Most analyzed patients, 92.6% (2742 of 2960), were derived from studies conducted in the Middle Eastern region, including Iran (8 studies, 1647 patients), 33 - 38 , 45 , 48 Iraq (1 study, 50 patients), 39 Israel (1 study, 105 patients), 40 Jordan (2 studies, 290 patients), 41 , 46 Lebanon (1 study, 273 patients), 50 and Saudi Arabia (5 studies, 423 patients). 42 - 44 , 47 , 51 Especially, 2 studies, 1 from Bahrain (172 patients) 49 and 1 from Saudi Arabia (46 patients), 43 did not provide information on the distribution of RAS mutations.…”

“…45 - 47 In 12 studies (15.7%, 3 of 19), 33 - 44 exon 2, 3, and 4 mutations of the KRAS gene were evaluated and whereas NRAS exons 2 and/or 3 were evaluated in 26.3% of studies. 45 - 47 , 50 , 51 Most studies (94.7%, 18 of 19) 33 - 48 , 50 , 51 assessed KRAS mutations in exon 2 codons 12 and 13. BRAF gene mutations were analyzed in 21.1% (4 of 19) studies.…”

“…BRAF gene mutations were analyzed in 21.1% (4 of 19) studies. 48 - 51 Microsatellite instability was examined in a subset of these studies (15.7%, 3 of 19), whereas the remaining studies did not report on MSI. 33 , 37 , 49 One study from Bahrain (172 patients) did not mention specific exons genotyped.…”

“…Of the 19 included studies, 12 focused on KRAS mutations, 33 - 44 3 on KRAS and NRAS mutations, 45 - 47 1 on KRAS and BRAF mutations, 48 and 3 on KRAS, NRAS, and BRAF mutations. 49 - 51 Notably, 3 of these studies provided insight into MSI status, contributing to a more comprehensive understanding of the genetic landscape of CRC. 33 , 37 , 49 The original articles included in the present review were identified from various Middle Eastern countries, including Bahrain, 49 Iran, 33 - 38 , 45 , 48 Iraq, 39 Israel, 40 Jordan, 41 , 46 Lebanon, 50 and Saudi Arabia.…”

“…33 , 37 , 49 The original articles included in the present review were identified from various Middle Eastern countries, including Bahrain, 49 Iran, 33 - 38 , 45 , 48 Iraq, 39 Israel, 40 Jordan, 41 , 46 Lebanon, 50 and Saudi Arabia. 42 - 44 , 47 , 51 After reviewing the relevant literature, we present the descriptive patterns between RAS mutation status and the descriptive clinicopathological characteristics of CRC patients in the collected studies which are explained below.…”