DMBT1 polymorphisms: Relationship to malignant glioma tumorigenesis

Hikaru Sasaki, Rebecca A. Betensky, J. Gregory Cairncross, D. N. Louis

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The deleted in malignant brain tumors 1 (DMBT1) gene on 10q25-26 is a candidate tumor suppressor gene in malignant gliomas, but its role is controversial, e.g., some DMBT1 homozygous deletions reflect unmasking of constitutional deletion polymorphisms by 10q loss. To clarify the role of DMBT1 in gliomagenesis, we investigated three reported deletion hot spots. Homozygous deletions at DMBT1 repeat 2-4 to 2-7 were found in 10 of 73 gliomas with 10q loss, but all 10 deletions reflected unmasking of constitutional hemizygous deletions. Alleles bearing deletion 2-4/2-7 were not selected significantly for by 10q loss, with retention of only 10 of 16 deleted alleles. No homozygous deletion was detected at locus 74k in the 5′ upstream region of DMBT1, and four tightly linked polymorphisms were found around this region; chromosome 10q loss randomly affected alleles with or without the variant sequences around locus 74k. Moreover, no significant selection pressure was detected for the haplotype with both deletion 2-4/2-7 and 5′ polymorphisms. There was no segregation of deletion 2-4/2-7 in glioma patients compared with unrelated individuals from reference families but a suggestion of a difference in the distribution of the 5′ polymorphisms between the reference individuals and glioma patients. Constitutional polymorphisms at DMBT1 repeat 2-9/2-10 appeared common in patients with both benign brain tumors and gliomas. A homozygote for both the 2-4/2-7 deletion and the 5′ polymorphisms had a glioma arise at a typical age and without an apparent family cancer predisposition. These data suggest that DMBT1 polymorphisms are not likely primary targets of 10q loss in malignant gliomas and do not support a major role for DMBT1 in gliomagenesis.

Original languageEnglish
Pages (from-to)1790-1796
Number of pages7
JournalCancer Research
Volume62
Issue number6
Publication statusPublished - 2002 Mar 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sasaki, H., Betensky, R. A., Cairncross, J. G., & Louis, D. N. (2002). DMBT1 polymorphisms: Relationship to malignant glioma tumorigenesis. Cancer Research, 62(6), 1790-1796.