Poster
Novel KRAS gene mutations in Saudi colorectal cancer patients


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Publication Details
Author list: Walid M. Naser, Mohamed A. Shawarby, Dalal M. Al-Tamimi, Arun Seth, Abdulaziz Al-Quorain, Areej M. Al-Nemer and Omar M. E. Albagha
Publication year: 2014
Journal: Pathology-Journal of the RCPA
Journal name in source: Pathology-Journal of the RCPA
Volume number: 46
Issue number: Supplement 2
Start page: S115
End page: S116
Web of Science ID:
PubMed ID:
Scopus ID:


We report 7 novel KRAS gene mutations discovered while retrospectively studying the prevalence and pattern of KRAS mutations in cancerous tissue obtained from 56 Saudi colorectal cancer patients from the Eastern Province.

Methods

Genomic DNA was extracted from paraffin-embedded, formalin-fixed cancerous and noncancerous colorectal tissues. A nested PCR approach was implemented. Successful and specific PCR products were then bi-directionally sequenced. The functional impact of the novel mutations on the K-ras protein was assessed using bioinformatics tools and molecular modeling.

Results

KRAS gene mutations were detected in the cancer tissue of 24 out of 56 cases studied. Of these, 11 were in exon 4 (19.64%). The 11 cases with exon 4 aberrations harbored 8 different mutations. All of these except two altered the K-ras protein amino acid sequence and all except one were novel as revealed by COSMIC database. The detected novel mutations were found to be somatic. The molecular modeling data fit with the prediction from Polyphen-2 (polymorphism phenotyping v2) and SIFT (sorting intolerant from tolerant tools), as well as conservation data. One mutation is predicted to be benign and modeling also showed little predicted effect on protein structure. The remaining mutations are predicted to cause substantial changes in the protein structure in line with the predicted damaging effect by polyphen-2 software. Of these, the Q150X nonsense mutation is the second truncating mutation to be reported in colorectal cancer in the literature.1

Conclusions

Our discovery of novel exon 4 KRAS mutations that are, so far, unique to Saudi patients from the Eastern Province may be attributed to environmental factors and/or racial/ethnic variations due to genetic differences. Alternatively, it may be related to the paucity of clinical studies on mutations other than those in codons 12, 13, 61 and 146. Further KRAS testing on a large number of patients, particularly beyond the most common hotspot alleles in exons 2 and 3, is needed to assess the prevalence and explore the exact prognostic and predictive significance of the discovered novel mutations as well as their possible role in colorectal carcinogenesis.


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Last updated on 2019-12-05 at 12:56