title: Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.
abstract: Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.
authors: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors: Inês
authors: I
authors: Crespo
authors: Ana Luísa
authors: AL
authors: Vital
authors: Ana Belen
authors: AB
authors: Nieto
authors: Olinda
authors: O
authors: Rebelo
authors: Hermínio
authors: H
authors: Tão
authors: Maria Celeste
authors: MC
authors: Lopes
authors: Catarina Resende
authors: CR
authors: Oliveira
authors: Pim J
authors: PJ
authors: French
authors: Alberto
authors: A
authors: Orfao
authors: María Dolores
authors: MD
authors: Tabernero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage / Q000235:genetics; D019942:Genes, p16; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D008869:Microtubule-Associated Proteins; D066246:ErbB Receptors