A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors

Olga B. Chernova, Robert P.T. Somerville, John Kenneth Cowell

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Loss of heterozygosity for 10q23-26 is seen in over 80% of glioblastoma multiforme tumors. We have used a positional cloning strategy to isolate a novel gene, LGI1 (Leucine-rich gene-Glioma Inactivated), which is rearranged as a result of the t(10;19)(q24;q13) balanced translocation in the T98G glioblastoma cell line lacking any normal chromosome 10. Rearrangement of the LGI1 gene was also detected in the A172 glioblastoma cell line and several glioblastoma tumors. These rearrangements lead to a complete absence of LGI1 expression in glioblastoma cells. The LGI1 gene encodes a protein with a calculated molecular mass of 60 kD and contains 3.5 leucine-rich repeats (LRR) with conserved flanking sequences. In the LRR domain, LGI1 has the highest homology with a number of transmembrane and extracellular proteins which function as receptors and adhesion proteins. LGI1 is predominantly expressed in neural tissues, especially in brain; its expression is reduced in low grade brain tumors and it is significantly reduced or absent in malignant gliomas. Its localization to the 10q24 region, and rearrangements or inactivation in malignant brain tumors, suggest that LGI1 is a candidate tumor suppressor gene involved in progression of glial tumors.

Original languageEnglish (US)
Pages (from-to)2873-2881
Number of pages9
JournalOncogene
Volume17
Issue number22
DOIs
StatePublished - Dec 3 1998

Fingerprint

Glioblastoma
Brain Neoplasms
Down-Regulation
Leucine
Genes
Glioma
Cell Line
Neoplasms
Chromosomes, Human, Pair 10
Proteins
Gene Rearrangement
Conserved Sequence
Loss of Heterozygosity
Tumor Suppressor Genes
Neuroglia
Organism Cloning
Brain

Keywords

  • Chromosome translocation
  • Gene rearrangements
  • Glioma
  • Human chromosome 10
  • Leucine-rich repeat
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors. / Chernova, Olga B.; Somerville, Robert P.T.; Cowell, John Kenneth.

In: Oncogene, Vol. 17, No. 22, 03.12.1998, p. 2873-2881.

Research output: Contribution to journalArticle

Chernova, Olga B. ; Somerville, Robert P.T. ; Cowell, John Kenneth. / A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors. In: Oncogene. 1998 ; Vol. 17, No. 22. pp. 2873-2881.
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