Chromosome 7 rearrangements in glioblastomas; loci adjacent to EGFR are independently amplified.
The first gene found to be amplified in human glioblastomas was EGFR at 7p12. More recently the MET gene at 7q31 was also reported amplified. We have studied chromosome 7 in a series of 47 glioblastomas by FISH, RFLP and microsatellite analysis. Four per cent (2/47) had 1 centromere, 26% (12/47) 2, 32% (15/47) 3, 4% (2/47) 4, and 34% (16/47) had subpopulations with variable numbers of chromosome 7 centromeres. In 25 of the 47 tumors (53%) the pattern of allelic imbalance observed at each informative locus was similar and in accord with the FISH data, indicating loss or gain of complete chromosome copies. In 32% of tumors (15/47) varying allelic imbalance was seen at different loci along the chromosome indicative of loss or gain of parts of chromosome 7 on a background of disomy, trisomy, tetrasomy, or polysomy. Amplification was studied in an extended series of 121 glioblastomas, and was seen at the 7p12 region in 47 tumors (39%). Forty-two tumors showed amplification of EGFR and 12 of these had extensive amplicons including a number of adjacent loci, always involving only 1 allele. The amplicons of 5 tumors (11%) did not include EGFR, indicating that other unidentified genes in the region are targeted for amplification. Amplification of MET was not found. The findings show that copy number changes of chromosome 7 are common and that a number of genes may be targeted for amplification at 7p12 in glioblastomas.
Liu
L
L
Ludwig Institute for Cancer Research and Unit of Tumor Pathology, Karolinska Hospital, Stockholm, Sweden.
Ichimura
K
K
Pettersson
E H
EH
Collins
V P
VP
D000483:Alleles; D002503:Centromere / Q000502:physiology; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D015321:Gene Rearrangement; D018773:Genes, erbB-1; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D020794:Receptor Protein-Tyrosine Kinases