Molecular gate keepers succumb to gene aberrations in colorectal cancer in Kashmiri population, revealing a high incidence area

Colorectal cancer [CRC] is one of the leading malignancies worldwide and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study was to identify p53 and K-ras gene mutations in CRC patients in a Kashmiri population, and to assess whether these mutations are linked with clinicopathological parameters. Paired tumor and normal tissue samples from a consecutive series of 53 patients undergoing resective surgery for CRC were prospectively studied for p53 and K-ras gene mutations by PCR/single strand conformation polymorphism [SSCP]. Less than half [45%, 19/42] of the patients presented mutations in the p53 gene. Twenty eight mutations were found in the p53 gene, which comprised of 23 substitutions [17 transitions + 6 transversions], and five insertions. The 23 substitutions constituted 18 missense mutations, two nonsense mutations, and three silent mutations. Of the 28 mutations [7.14%] observed in this study, 2 were not previously reported for CRC samples and were identified as novel p53 mutations. A few patients [22.64%, 12/53] presented with mutations in K-ras, constituting 13 missense mutations, out of which 11 were G-A transitions, one was a G-C transversion, and one a G-T transversion. More than half [61.5%] of the mutations occurred in codon 12 whereas a few [38.5%] occurred in codon 13. One tumor contained missense mutations in both codons. Comparison of the mutation profiles of our patients with those of other ethnic populations and regions reflected both differences and similarities, indicating co-exposure to a unique set of risk factors. Mutations of the p53 and K-ras genes are some of the most common genetic changes in the development of human CRC. The high frequency of p53 gene mutations implicates p53 as a predominant factor for CRC in the high-risk ethnic Kashmiri population

Mutations in epidermal growth factor receptor gene in esophageal squamous cell carcinoma patients in Kashmir: a high incidence area of India

Activating mutations in Epidermal Growth Factor Receptor [EGFR] are common in lung adenocarcinoma of never smokers but are rare in other types of cancer. Here we have analysed mutations in exons 19 to 21 of EGFR and in exons 19 and 20 of the EGFR homolog HER2 in 54 cases of Esophageal Squamous Cell Carcinomas [ESCC] from patients recruited in Kashmir, India, a region of high incidence for this cancer. We report the detection of 3 mutations [6%] in the ATP- binding regulatory loops of the tyrosine kinase domain of EGFR [deletion 746-750, p753L, G719D]. No mutation was found in HER2. This is the first report of activating EGFR mutations in ESCC, of the same type as those detected in lung adenocarcinoma of never-smokers. This suggests that a small portion of ESCC patients in this high incidence area may benefit from treatment with EGFR tyrosine kinase inhibitors