The integrated landscape of driver genomic alterations in glioblastoma
By V. Frattini, V. Trifonov, Joseph Chan, Angelica M. Castano, M. Lia, F. Abate, S. Keir, A. Ji, P. Zoppoli, F. Niola and 19 more. Nature Genetics, 2013
510 citations recorded by the source corpus.
Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma. We found mutations with loss of heterozygosity in LZTR1, encoding an adaptor of CUL3-containing E3 ligase complexes. Mutations and deletions disrupt LZTR1 function, which restrains the self renewal and growth of glioma spheres that retain stem cell features. Loss-of-function mutations in CTNND2 target a neural-specific gene and are associated with the transformation of glioma cells along the very aggressive mesenchymal phenotype. We also report recurrent translocations that fuse the coding sequence of EGFR to several partners, with EGFR-SEPT14 being the most frequent functional gene fusion in human glioblastoma. EGFR-SEPT14 fusions activate STAT3 signaling and confer mitogen independence and sensitivity to EGFR inhibition. These results provide insights into the pathogenesis of glioblastoma and highlight new targets for therapeutic intervention.
Subfields: Cancer Research, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2d7a8b08438cba31d5d2323a516072dd97e9a98d
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In Genetics
Citations in the corpus
- Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma (2017, unknown): “…addition, a subset of cells from the same patient carry a CCNL1 frameshift mutation in exon 11 resulting in deletion of the stop codon as well as a missense mutation (c.C1748T:p.T583I) in BCOR, a gene which has previously been shown to be somatically mutated in glioblastoma (Frattini et al., 2013).”
- Glioblastoma: pathology, molecular mechanisms and markers (2015, background): “The mesenchymal signature is mainly regulated by the expression of the transcription factor signal transducer and activator of transcription 3 (STAT3), CCAAT/enhancer-binding protein-β (C/EBPβ), and transcriptional co-activator with PDZ-binding motif (TAZ), which have also been associated with poor ”
- Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma (2017, unknown): “LZTR1 germline mutations have been associated with inherited segmental schwannomatosis, and somatic LTZR1 mutations are identified as driver mutations in glioblastoma (Frattini et al., 2013; Piotrowski et al., 2014).”