A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.
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.
Chernova
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OB
Department of Neurosciences NC30, The Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
Somerville
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RP
Cowell
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JK
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D001932:Brain Neoplasms / Q000235:genetics* / Q000556:secondary; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D017124:Conserved Sequence; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000090263:Leucine-Rich Repeat Proteins; D008969:Molecular Sequence Data; D008970:Molecular Weight; D005810:Multigene Family; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins