Frequent DNA methylation but not mutation of the ID4 gene in malignant lymphoma.

ID4 is a member of the inhibitor of DNA binding (ID) family, and inhibits the binding of basic helix-loop-helix transcription factors to DNA. In some malignant tumors, ID4 is inactivated by promoter hypermethylation, and is thought to be a candidate tumor suppressor gene (TSG). We have found that the promoter region of the ID4 gene is frequently methylated in lymphoid cell lines (100%, 9/9), primary diffuse large B-cell lymphoma (95%, 19/20), and follicular lymphoma (100%, 10/10). Somatic mutation of the ID4 gene was also examined, and no mutations were found. These findings suggest that the ID4 gene might be inactivated by DNA hypermethylation, and may function as a TSG in malignant lymphoma.