title: Genome-wide allelic imbalance analysis of pediatric gliomas by single nucleotide polymorphic allele array.
abstract: Using single nucleotide polymorphic (SNP) allele arrays, we analyzed 28 pediatric gliomas consisting of 14 high-grade gliomas and 14 low-grade gliomas. Most of the low-grade gliomas had no detectable loss of heterozygosity (LOH) in any of the 11,562 SNP loci; exceptions were two gangliogliomas (3q and 9p), one astrocytoma (6q), and two subependymal giant cell astrocytomas (16p and 21q). On the other hand, all high-grade gliomas had various degrees of LOH affecting 52 to 2,168 SNP loci on various chromosomes. LOH occurred most frequently in regions located at 4q (54%), 6q (46%), 9p (38%), 10q (38%), 11p (38%), 12 (38%), 13q (69%), 14q (54%), 17 (38%), 18p (46%), and 19q (38%). We also detected amplifications of epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor alpha (PDGFRalpha) in a few of the 13 cases of glioblastoma multiforme analyzed. Interestingly, the amplified EGFR and PDGFRalpha were located within regions of LOH. SNP loci with LOH and copy number changes were validated by sequencing and quantitative PCR, respectively. Our results indicate that, in some pediatric glioblastoma multiforme, one allele each of EGFR and PDGFRalpha was lost but the remaining allele was amplified. This may represent a new molecular mechanism underlying tumor progression.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. kkwong@mdanderson.org
authors.forename: Kwong-Kwok
authors.initials: KK
authors.lastname: Wong
authors.forename: Yvonne T M
authors.initials: YT
authors.lastname: Tsang
authors.forename: Yi-Mieng
authors.initials: YM
authors.lastname: Chang
authors.forename: Jack
authors.initials: J
authors.lastname: Su
authors.forename: Angela M
authors.initials: AM
authors.lastname: Di Francesco
authors.forename: Daniela
authors.initials: D
authors.lastname: Meco
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
authors.forename: Laszlo
authors.initials: L
authors.lastname: Perlaky
authors.forename: Robert C
authors.initials: RC
authors.lastname: Dauser
authors.forename: Adekunle
authors.initials: A
authors.lastname: Adesina
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Bhattacharjee
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Ching C
authors.initials: CC
authors.lastname: Lau
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D066246:ErbB Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha