title: Gene expression profiles of human glioblastomas are associated with both tumor cytogenetics and histopathology.
abstract: Despite the increasing knowledge about the genetic alterations and molecular pathways involved in gliomas, few studies have investigated the association between the gene expression profiles (GEP) and both cytogenetics and histopathology of gliomas. Here, we analyzed the GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas, and 2 mixed tumors) and their association with tumor cytogenetics and histopathology. Unsupervised and supervised analyses showed significantly different GEP in low- vs high-grade gliomas, the most discriminating genes including genes involved in the regulation of cell proliferation, apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma multiforme (GBM), 3 subgroups of tumors were identified according to their GEP, which were closely associated with the cytogenetic profile of their ancestral tumor cell clones: (i) EGFR amplification, (ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary, our results show a clear association between the GEP of gliomas and tumor histopathology; additionally, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Further studies in larger series of patients are necessary to confirm our observations.
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Vital
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Tabernero
authors.forename: Abel
authors.initials: A
authors.lastname: Castrillo
authors.forename: Olinda
authors.initials: O
authors.lastname: Rebelo
authors.forename: Hermínio
authors.initials: H
authors.lastname: Tão
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomes
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Nieto
authors.forename: Catarina
authors.initials: C
authors.lastname: Resende Oliveira
authors.forename: Maria Celeste
authors.initials: MC
authors.lastname: Lopes
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D016000:Cluster Analysis; D003582:Cytogenetics; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult