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BACKGROUND: One of the genetic alterations implicated in tumor progression in colorectal cancers (CRCs) are abnormalities in Kristen Rat Sarcoma (KRAS) gene. Evaluation of KRAS mutation status is an important prognostic factor and has predictive value in deciding first line therapy based on monoclonal antibodies such as Cetuximab and Panitumumab in metastatic CRCs. MATERIALS AND METHODS: In this retrospective study, we analyzed 7 different somatic mutations in Exon 2 of KRAS gene in 299 unselected incidental CRC patients who visited the hospital for clinical management during the period 2009–2013. Most of the tumors were primarily originating from colon and rectum; nevertheless, there were a few from rectosigmoid, sigmoid, ceacum and anal canal in the study group. Genomic DNA extracted from paraffin embedded tumor tissues was screened for 7 point mutations located in Codons 12 and 13 of KRAS gene, using Scorpions amplified refractory mutation system real time polymerase chain reaction technology. Statistical analysis was performed to assess bivariate relationship between different variables that includes: mutation status, mutation type, tumor location, tumor morphology, age and sex. RESULTS: Prevalence of mutation in Codons 12 and 13 was 42.8% in the study group. Well‑differentiated tumors had significantly more mutation positivity than moderately and poorly differentiated tumors (P = 0.001). 92% of the mutations were from Codon 12 and 8% in Codon 13. Glycine to Arginine was relatively more common in rectosigmoid followed by ceacum, while Glycine to Alanine mutation was relatively more prevalent in sigmoid, followed by rectum and rectosigmoid. CONCLUSION: The results suggest a prevalence of KRAS mutation at 42.8% in Indian population indicating that this testing is very crucial for targeted therapy management in metastatic CRC in India. Further analysis on mutation status of other homologues such as NRAS and downstream partner, v‑raf murine sarcoma viral oncogene homolog B1, would add value to understanding the role of anti‑epidermal growth factor receptor therapy in CRC management.
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The frequency and clinicopathologic significance of the K-ras gene point mutation in stomach cancer remain to be defined. We investigated the frequency of K-ras codon 12 point mutations in stomach cancer using a polymerase chain reaction (PCR)-based method in 94 samples and 100 age and sex matched controls. The overall frequency of K-ras codon 12 point mutations in stomach cancer was 3.19% (3/94). DNA sequencing of three cases with K-ras codon 12 point mutations identified a single-base substitution of GGT to GTT (glycine to valine) .Two of them were in heterozygous condition and one was in homozygous condition. Conclusions: K-ras codon 12 point mutations are uncommon in stomach cancer (3.19%) in Southern India.
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BACKGROUND: Many studies suggest that point mutations of ras oncogene develop tumors. The advantages of body fluid analysis are easy accessibility and more simple procedure than tissue specimen. So, we investigated the incidence of K-ras codon 12 mutation in body fluids of patients with malignant solid tumors and tried to define the significance of K-ras codon 12 mutation in body fluids. METHODS: We analyzed 58 specimens of body fluids in patients diagnosed as solid tumor. The first PCR products were digested with BstN1 and then followed the second PCR and BstN1 digestion. Nucleotide sequencing was performed by Sanger's method. RESULTS: The incidences of K-ras codon 12 mutation are 75% in biliary cancer, 50% in pancreatic cancer, 31% in lung cancer, 14% in liver cancer, and 8% in stomach cancer. Mutations of K-ras codon 12 were detected in 24% (9/37) of body fluids with malignant cells and 19% (4/21) of body fluids without malignant cells. The proportions of malignant cells were not different between the patients with and without K-ras codon 12 mutation in effusions with malignant cells. Nucleotide sequencing on one sample of a patient with pancreatic carcinoma revealed single base substitution in codon 12 of K-ras gene from GGT to GAT. CONCLUSIONS: The incidences of ras mutation in body fluids are variable with tumor type. Since K-ras codon 12 point mutation was highly specific, not in those of patients without tumors, examination of K-ras codon 12 point mutation may be an additive diagnostic tool for early detection of metastasis to body fluids.