Publication: Kras gene mutational profiles among colorectal cancer (CRC) patients in Hospital Universiti Sains Malaysia (USM)
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Date
2022
Authors
Hasbullah, Hidayati Husainy
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Abstract
Introduction The global burden of colorectal cancer (CRC) necessitates the development of a novel biomarker that aims to improve the detection, management and/or treatment outcomes of CRC patients. One such marker is the KRAS oncogene. Studies have shown that KRAS mutational status is a robust predictive marker for response to anti-EGFR monoclonal antibodies. Recently, FDA has approved the use of sotorasib, a KRAS-G12C protein inhibitor in non-small cell lung carcinoma patients with G12C mutations. The role of sotorasib in CRC is still under evaluation but has shown great potential. Despite extensive research worldwide, there is still limited data on the KRAS mutational profiles amongst CRC patients in Malaysia. This study aims to determine the proportion of CRC patients with KRAS mutations at codons 12 and 13 in HUSM, Kelantan located on the East Coast of Malaysia, and to ascertain if there is any correlation between known KRAS mutations and clinicopathological features of CRC. Methodology This is a cross-sectional, non-interventional genetic study involving CRC patients diagnosed in Hospital USM, Kelantan between 2018 and 2019. DNA was extracted from formalin-fixed, paraffin-embedded tissues of the primary CRC tumour (n=33) after informed consent was obtained. Codons 12 and 13 of the KRAS gene were amplified using the conventional polymerase chain reaction (PCR) method. The PCR products were outsourced to a commercial laboratory for DNA Sanger sequencing. Result Current study identified that the frequency of KRAS mutations at codons 12 and 13 was 36.4% (12/33). G12D (50.0%, 6/12) was the most common single point mutation observed followed by G12V (25.0%, 3/12); G13D (16.7%, 2/12) and G12S (8.3%, 1/12). No significant differences were observed in the distribution of gender, age and ethnicity between patients with mutant KRAS and wild-type KRAS (p = 0.469; p = 0.392; p = 0.630, respectively). There was also no correlation between KRAS mutations and tumour characteristics such as the stage and histological differentiation, location of the primary tumour and initial CEA level (p = 0.420; p = >0.950; p = 0.429, respectively). Conclusion A significant proportion of CRC patients in Hospital USM had KRAS mutations. This study is the first to demonstrate that the frequency of KRAS mutations is higher in our region compared to the previous studies conducted at the West Coast of Malaysia. The spectrum of KRAS mutations in the study cohort is consistent with previous reports. No association between KRAS mutations and any of the clinicopathological features of CRC patients was observed
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Keywords
Colorectal cancer , KRAS