Intratumoral patterns of genomic imbalance in glioblastomas.
Glioblastomas are morphologically and genetically heterogeneous, but little is known about the regional patterns of genomic imbalance within glioblastomas. We recently established a reliable whole genome amplification (WGA) method to randomly amplify DNA from paraffin-embedded histological sections with minimum amplification bias [Huang et al (J Mol Diagn 11: 109-116, 2009)]. In this study, chromosomal imbalance was assessed by array comparative genomic hybridization (CGH; Agilent 105K, Agilent Technologies, Santa Clara, CA, USA), using WGA-DNA from two to five separate tumor areas of 14 primary glioblastomas (total, 41 tumor areas). Chromosomal imbalances significantly differed among glioblastomas; the only alterations that were observed in > or =6 cases were loss of chromosome 10q, gain at 7p and loss of 10p. Genetic alterations common to all areas analyzed within a single tumor included gains at 1q32.1 (PIK3C2B, MDM4), 4q11-q12 (KIT, PDGFRA), 7p12.1-11.2 (EGFR), 12q13.3-12q14.1 (GLI1, CDK4) and 12q15 (MDM2), and loss at 9p21.1-24.3 (p16(INK4a)/p14(ARF)), 10p15.3-q26.3 (PTEN, etc.) and 13q12.11-q34 (SPRY2, RB1). These are likely to be causative in the pathogenesis of glioblastomas (driver mutations). In addition, there were numerous tumor area-specific genomic imbalances, which may be either nonfunctional (passenger mutations) or functional, but constitute secondary events reflecting progressive genomic instability, a hallmark of glioblastomas.
Nobusawa
Sumihito
S
International Agency for Research on Cancer, Lyon, France.
Lachuer
Joel
J
Wierinckx
Anne
A
Kim
Young Ho
YH
Huang
Jian
J
Legras
Catherine
C
Kleihues
Paul
P
Ohgaki
Hiroko
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D015203:Reproducibility of Results
D020796:Receptor, Platelet-Derived Growth Factor alpha; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
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