Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors

Abstract

DMBT1 has been implicated as a candidate tumor suppressor gene on chromosome 10q for brain, gastrointestinal and lung cancer. Homozygous deletion and lack of expression are 2 known mechanisms for inactivating DMBT1. We evaluated whether somatic mutation, which represents a major inactivation mechanism for most tumor suppressor genes, occurs in the DMBT1 gene. A total of 102 primary brain tumors, consisting of 25 glioblastoma multiforme, 24 medulloblastoma and 53 oligodendroglial tumors, were analyzed by conformation-sensitive gel electrophoresis in all 54 coding exons of DMBT1. Twelve different base substitutions were detected in 26 (25%) tumors. Eight base substitutions resulted in amino acid changes and 4 were silent. These base changes were also detected in tumor-matched blood samples, however, indicating that the base variations represent genetic polymorphisms. We also assessed homozygous deletions of the DMBT1 gene in the series and found that 16 of 95 (5 glioblastomas, 5 medulloblastomas, 6 oligodendroglial tumors; total 17%) tumors harbor such alteration. High-quality blood DNA samples were available in 5 tumors carrying homozygous deletion and, using long-range PCR, 3 of these blood samples showed germline hemizygous deletions in a region between introns 10 and 26 of DMBT1. Our results showed that mutation does not play a role in inactivation of DMBT1 in brain tumors. Intragenic homozygous deletion of DMBT1 is common in brain tumors and is likely a result of a germline deletion of 1 allele followed by loss of the second allele during tumor development.

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

“…There is a large body of literature supporting an association of DMBT1 with cancer (2,5,23,26,35,37). However, other studies have failed to provide a link between DMBT1 and cancer (20,40,41). We did not find evidence that a lack of Muclin caused gastrointestinal tumors.…”

The protective role of DMBT1 in cervical squamous cell carcinoma

“…Consistent with our finding, both the mRNA and protein levels of DMBT1 were determined to be lower in CSCC tissues than that in the adjacent normal tissues after examination of qRT‐PCR and Western blot methods, demonstrating a tumor suppressor role in CSCC. Notably, the downregulation of DMBT1 in many tumor cell lines and primary tumors has been reported to be possibly associated with allele loss, homozygous deletion, base substitution, structural rearrangement, or promoter methylation according to the previous studies, but its detailed mechanism of DMBT1 downexpression in CSCC has not been clarified, which would explore in our future research.…”

Quantitative proteomic profiling of the extracellular matrix of pancreatic islets during the angiogenic switch and insulinoma progression

“…In agreement with this, we observed that the abundance of decorin significantly decreases at the angiogenic switch and is even further decreased in advanced insulinoma. Dmbt1 has been shown to be deleted or mutated in various tumor types41424344. Future work will be required to evaluate whether hemicentin or Vwa5a play functional roles in cancer progression and the angiogenic switch.…”