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[Cancer Research 61, 4556-4560, June 1, 2001]
© 2001 American Association for Cancer Research

Regular Articles

Loss of Expression and Aberrant Methylation of the CDH13 (H-Cadherin) Gene in Breast and Lung Carcinomas1

Kiyomi O. Toyooka, Shinichi Toyooka, Arvind K. Virmani, Ubaradka G. Sathyanarayana, David M. Euhus, Michael Gilcrease, John D. Minna and Adi F. Gazdar2

Hamon Center for Therapeutic Oncology Research [K. O. T., S. T., A. K. V., V. G. S., A. F. G.] and Departments of Pathology [A. V. K., A. F. G.], Surgery [D. M. E.], Internal Medicine [J. D. M.], and Pharmacology [J. D. M.], University of Texas Southwestern Medical Center, Dallas, Texas 75390, and Department of Pathology, M. D. Anderson Medical Center, Houston, Texas 77030 [M. G.]

Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2–3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell lung cancer cell lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CDH13expression was present in 24 of 30 (80%) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5'-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.




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