Aberrant signature patterns of ATM, γ-H2AX and p53 proteins in the patients exposed to methyl isocyanate diagnosed with gallbladder cancer
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Date
2014-04-29
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Plovdiv University Press “Paisii Hilendarski”
Abstract
Cancer of gallbladder is a hidden phenomenon and highly malignant with underprivileged diagnosis and poor survival. Study of cancer patterns amongst victims of Bhopal gas tragedy exposed to methyl isocyanate revealed higher incidence of gallbladder cancer that necessitated a more objective elucidation of the disease at its molecular level. Tissues of 92 cases of gallbladder cancer patients were taken in the study (31 men and 61 women, age range 16–85 years, mean age 45.8±1.50 years). Mutations of ATM, γ-H2AX and p53 were predominantly seen in the methyl isocyanate exposed cohort diagnosed with adenocarcinoma, with 61.4% (43/70), 54.3% (38/70) and 73% (51/70) respectively, involving infiltration into the papillary and mucinous region/cell types of the gallbladder. Out of these, the expression frequency of all the above three genes was higher in moderately differentiated adenocarcinoma in comparison to poorly and well-differentiated ones. The results of the present study support the hypothesis that ATM and p53 mutations provide fundamental genetic signatures influencing tumor behavior across patient subsets and invasiveness of the disease, while γ-H2AX is apparently an ordinary pathway involved in the genesis of tumors.
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ATM, p53, γ-H2AX, gallbladder adenocarcinoma, adenosquamous carcinoma, adenoma with dysplasia