Genetic alteration in the short telomere lesion as a precancerous lesion of gastric cancer

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Telomere is shortened in gastric cancer. A semi-quantitative and geographic analysis of telomere in non-cancerous gastric mucosa showed the localized mucosal area with shortened telomere, which was named as short telomere lesion(STL)". In this project, specific genetic alterations in STL were examined. TDGF-2, which is one of pseudogene of CR-1, was deleted in high frequency in STL. TDGF-2 gene product inhibited the physical association of CR-1 and Nodal. The lack of TDGF-2 as a CR-1 negative regulator induced activation of CR-1-Nodal pathway, which might provoke stem cell hyperplasia in gastric epithelium. A variant type of CTP2D6 was expressed in STL, which might affect the metabolism of genotoxic substances.