DMBT1 homozygous deletion in diffuse astrocytomas is associated with unfavorable clinical outcome

Kazuya Motomura, Michel Mittelbronn, Werner Paulus, Benjamin Brokinkel, Kathy Keyvani, Ulrich Sure, Karsten Wrede, Yoichi Nakazato, Yuko Tanaka, Daniela Pierscianek, Young Ho Kim, Luigi Mariani, Anne Vital, Hiroko Ohgaki*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

Primary glioblastomas develop with a short clinical history, without evidence for less malignant precursor lesions, while secondary glioblastomas slowly develop via progression from diffuse astrocytoma (WHO grade II) or anaplastic astrocytoma (WHO grade III). The time until progression and the clinical outcome of diffuse astrocytomas vary significantly. We have shown that IDH1 mutations reliably distinguish between primary glioblastomas (without IDH1 mutations) and secondary glioblastomas (with IDH1 mutations). The most frequent genetic alteration shared by primary and secondary glioblastomas is loss of heterozygosity at 10q (up to 60% of cases). Here, we first assessed The Cancer Genome Atlas data to identify gene loss at 10q in glioblastomas with or without IDH1 mutations. Using log-ratio thresholds of-1.0, 10 genes were identified; with the log-ratio thresholds of-2.0, only the DMBT1 (deleted in malignant brain tumor 1) gene at 10q26.13 remained as a deleted gene in glioblastomas with or without IDH1 mutations (12.5% vs 8.0%). We then analyzed a total of 404 gliomas by differential polymerase chain reaction and found a DMBT1 homozygous deletion at a similar frequency in primary and secondary glioblastomas (19.6% vs 20.8%). A fraction (11.3%) of diffuse astrocytomas showed a DMBT1 homozygous deletion that was significantly associated with a shorter overall survival (52.8 vs 84.0 months; p = 0.003). These results indicate that a DMBT1 homozygous deletion is present in a fraction of diffuse astrocytomas and that it is associated with an unfavorable clinical outcome.

Original languageEnglish
Pages (from-to)702-707
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume71
Issue number8
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

Keywords

  • DMBT1
  • Diffuse astrocytoma
  • IDH1
  • Primary glioblastoma
  • Secondary glioblastoma

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