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Genetic Alterations of Candidate Tumor Suppressor ING1 in Human Esophageal Squamous Cell Cancer¹

First Department of Surgery [L. C., N. M., T. N., N. H., Y. S., Y. N., H. I., N. T.], Department of Pathology [T. Y.], Okayama University Medical School, Okayama 700-8558, Japan, and Department of Medical Biochemistry and Southern Alberta Cancer Research Center, The University of Calgary, Calgary, Alberta, T2N 4N1 Canada [K. R.]

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33–34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33–34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

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