Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors.
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.
Pang
Jesse Chung-Sean
JC
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
Dong
Zhiqian
Z
Zhang
Rong
R
Liu
Yanhui
Y
Zhou
Liang-Fu
LF
Chan
Bik Wan
BW
Poon
Wai Sang
WS
Ng
Ho-Keung
HK
D000373:Agglutinins; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D002135:Calcium-Binding Proteins; D002879:Chromosomes, Human, Pair 10; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D005091:Exons; D017353:Gene Deletion; D005909:Glioblastoma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007438:Introns; D008527:Medulloblastoma / Q000235:genetics*; D009154:Mutation; D009690:Nucleic Acid Conformation; D009837:Oligodendroglioma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D013696:Temperature; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D004247:DNA