"RAS Mutations in Colorectal Cancer in Tunisian Population"

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Anti-EGFR therapy is currently one of the targeted therapies for metastatic CRC. Mutations in the RAS gene are predictive of poor response to anti-EGFR. Approximately 50-60% of CRCs have a RAS mutation with KRAS being the most frequently mutated gene. We aimed to analyse RAS mutations, using Idylla KRAS and NRAS mutation test, in CRC to determine the group of patients potentially candidates for anti-EGFR therapy. Besides, we tried to identify statistically significant associations between some clinicopathological parameters and the different types of KRAS mutations detected. Methods: A series of 119 cases of CRC was enrolled the Pathology department of Salah Azaiez Institute of Tunis from 02 April 2021 to 01 November 2021. Idylla KRAS and NRAS mutation test detected 21 mutations on the KRAS gene (exons 2, 3 and 4) and 18 mutations on the NRAS gene (exons 2, 3 and 4).Results: RAS gene mutations were found in 54% of cases, mainly of KRAS type (98.4%). For KRAS mutations, exon 2 mutations were found in 87.3%, followed by exon 4 (8%) and exon 3 (4.7%). Mutations in exon 2 involved codon 12 (56% G12D, 23.2% G12V, 9.3% G12C, 4.6% G12A, 4.6% G12S, 2.3% G12R) in 68% and codon 13 (G13D then G13V) in 32%. Mutations in exon 3 concerned codon 61 (the Q61H mutation followed by the Q61RL mutation). Mutations in exon 4 affected codon 146 (the A146P/T/V mutation). The only NRAS mutation found was a G12D mutation. Our work revealed that statistically, the presence of KRAS mutations was significantly associated to male patients (p=0.03) on one hand and to the presence of distant metastasis (p=0.03) on the other hand. Conclusion:Ras gene mutations seem to play a pivotal role in the resistance to anti-EGFR monoclonal antibodies in CRC treatments. Thus, testing for these mutations has become essential to select eligible candidates to benefit from this targeted therapy without unwarranted toxicity and expenses.