An integrative model on the role of DMBT1 in epithelial cancer

The gene, deleted in malignant brain tumors 1 (DMBT1), has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumor suppressor gene. We have proposed that its presumptive dual function in protection and differentiation is of importance to understand its role in cancer. To gain insights into its role in tumorigenesis, we conducted a comprehensive study on DMBT1 mutations, expression and location. Twenty-one out of 44 tumors showed variable numbers of tandem repeats (VNTRs) due to genetic polymorphism of DMBT1, whereas 11 out of 44 tumors displayed presumable mutations. However, none of the alterations would be predicted to lead to a complete inactivation of the gene. DMBT1 is mucin-like and shows tissue-specific expression and secretion, pointing to a function in the protection of monolayered epithelia and to an additional function in the differentiation of multilayered epithelia. The expression patterns in carcinomas arising from the respective structures support this view. Accepting this functional dualism gives rise to an initial model on the role of DMBT1 in epithelial cancer.