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Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors
Author(s) -
Pang Jesse Chungsean,
Dong Zhiqian,
Zhang Rong,
Liu Yanhui,
Zhou Liangfu,
Chan Bik Wan,
Poon Wai Sang,
Ng Hokeung
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11019
Subject(s) - oligodendroglial tumor , biology , medulloblastoma , tumor suppressor gene , oligodendroglioma , exon , germline mutation , cancer research , mutation , gene , allele , glioma , germline , brain tumor , microbiology and biotechnology , genetics , pathology , carcinogenesis , astrocytoma , medicine
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. © 2003 Wiley‐Liss, Inc.