Genome-wide allelic imbalance analysis of pediatric gliomas by single nucleotide polymorphic allele array.
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.
Wong
Kwong-Kwok
KK
Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. kkwong@mdanderson.org
Tsang
Yvonne T M
YT
Chang
Yi-Mieng
YM
Su
Jack
J
Di Francesco
Angela M
AM
Meco
Daniela
D
Riccardi
Riccardo
R
Perlaky
Laszlo
L
Dauser
Robert C
RC
Adesina
Adekunle
A
Bhattacharjee
Meenakshi
M
Chintagumpala
Murali
M
Lau
Ching C
CC
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
D066246:ErbB Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha