Extended RAS mutations (KRAS and NRAS) in patients with colorectal cancers in eastern India

Abstract

Background: All treatment guidelines currently mandate KRAS and NRAS mutation analysis as a pretreatment workup of colorectal cancers (CRCs), in view of their prognostic and predictive significance. Objectives: In this study, we aimed to assess the prevalence of the extended-spectrum of KRAS and NRAS mutations in patients with CRCs from Kolkata, in eastern India. Materials and Methods: This retrospective observational study was conducted from January 2017 to January 2020 in patients registered for treatment at the IPGMER and SSKM Hospitals, in Kolkata, India. Patients diagnosed with CRCs with adenocarcinoma histology were included in the study. The formalin-fixed paraffin-embedded tumor tissues of the patients were assessed for the extended-spectrum of KRAS and NRAS mutations using a real-time polymerase chain reaction. The cut-off used for “Tumor Not Present” (TNP) reporting was 15%. These mutations were then mapped with the tumor location. Data were analyzed in a de-identified manner, using simple descriptive statistical methods. The two-tailed Fisher's exact test was used to determine any statistically significant association between variables. Results: TNP was reported in 13 (8.12%). A total of 147 patients with CRC were included in the study. Extended RAS mutations were found in 59 (40.1%) patients. KRAS and NRAS were found to be mutated in 55 (37.4%) and 4 (2.7%) patients, respectively. The most common mutation in KRAS was in G12 in exon 2 (34, 61.8%). Followed by Q61 in exon 3 (8, 14.5%) and A146 in exon 4 (8, 14.5%). Half of the NRAS mutations were in codons 12–13 in exon 2 and half were in codon 61 in exon 3. Dual KRAS mutations were observed in one patient, while two patients had both a KRAS and an NRAS mutation. Extended RAS, KRAS, and NRAS mutations were numerically more common in right-sided CRCs (47.2%, 43.4%, and 3.8%, respectively) than in left-sided CRCs (37.2%, 34%, and 2.1%, respectively). The rectum had numerically higher extended RAS and KRAS mutations but lower NRAS mutations (43.1%, 41.37%, and 1.72% respectively) as compared to the colon (37.36%, 34.06%, and 3.29% respectively). Conclusions: Extended RAS mutations are present in about 40% of the patients with CRC in eastern India, with KRAS (37.4%) mutations more prevalent than NRAS (2.7%) mutations. The right-sided CRCs have predictably more RAS mutations than the left.