Correlation between KRAS, NRAS and BRAF mutations and tumor localizations in patients with primary and metastatic colorectal cancer

Abstract

IntroductionDetection of abnormalities in the KRAS, NRAS and BRAF genes is extremely important for proper qualification of colorectal cancer (CRC) patients for therapy with anti-EGFR monoclonal antibodies. However, data about prevalence of mutations in these genes, in different localizations of CRC tumors, is limited.Material and methodsWe examined the frequency of mutations in the KRAS, NRAS and BRAF genes in 500 Caucasian CRC patients (200 women and 300 men, median age – 66 years). DNA was isolated from formalin- fixed, paraffin embeded (FFPE) tissues using Qiagen QIAmp DNA FFPE-kit. Analysis of mutations was carried out using KRAS/BRAF, NRAS and BRAF Mutation Analysis Kit for Real-Time PCR (EntroGen) using the Cobas 480 real-time PCR apparatus (Roche Diagnostics)ResultsKRAS mutations have been detected in 190 patients (38%), NRAS mutations in 20 patients (4%), whereas BRAF mutations in 24 patients (4,8%). There were no associations between age of CRC patients and frequency of KRAS, NRAS and BRAF genes mutations. These mutations were significantly more often diagnosed in women (55.5%) than in man (41%, p<0.005). Tumors of rectum and sigmoideum were the most often observed in both groups of CRC patients – with and without KRAS, NRAS and BRAF genes mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutationsConclusionsOur study showed that the occurrence of mutations in the KRAS, NRAS and BRAF genes is not accidental and depends on the location of CRC tumors.

Clinical Characterization of Targetable Mutations (BRAF V600E and KRAS G12C) in Advanced Colorectal Cancer—A Nation-Wide Study

“…A study on non-metastatic CRC patients found the mutation in 2/163 (1.22%) cases [16]. Two Polish studies on advanced CRC reported the incidence of BRAF V600E mutations in 24/500 (4.80%) and 7/102 (6.86%), respectively [17,18]. A recently published large study on the Russian population reported the incidence at 6.7% [19].…”

Concurrent NRAS-BRAF variants in metastatic colorectal cancer: a Tunisian case report

“…It is important to note that KRAS, NRAS and BRAF belong to the same signalling pathway, which makes the co-occurrence of their mutations extremely rare, as they are considered to be mutually exclusive. In fact, there is very little information on the biological behaviour of tumours with concurrent KRAS/BRAF mutations [8]. However, some studies have reported these concomitant mutations in KRAS and/or NRAS and BRAF presenting it as an indication of a poor prognosis.…”

Preliminary Exploration of Structure–Function Crosstalk in Colorectal Cancer Research: Protein Structuromics

“…To better understand CRC development, traditional research has focused on protein mutations, such as KRAS, NRAS and BRAF mutations 20 , and on DNA or RNA sequencing analysis. We believe that including DNA and RNA mutations, isoform appearance, and variant new versions will contribute to translating genotype into phenotype, and changes in status should be shown after related proteins are activated.…”