Genomic aberrations in 80 cases of primary glioblastoma multiforme: Pathogenetic heterogeneity and putative cytogenetic pathways.
Screening the whole glioblastoma multiforme (GBM) genome for aberrations is a good starting point when looking for molecular markers that could potentially stratify patients according to prognosis and optimal treatment. We investigated 80 primary untreated GBM using both G-banding analysis and high-resolution comparative genomic hybridization (HR-CGH). Abnormal karyotypes were found in 83% of the tumors. The most common numerical chromosome aberrations were +7, -10, -13, -14, -15, +20, and -22. Structural abnormalities most commonly involved chromosomes 1 and 3, and the short arm of chromosome 9. HR-CGH verified these findings and revealed additional frequent losses at 1p34-36, 6q22-27, and 19q12-13 and gains of 3q26 and 12q13-15. Although most karyotypes and gain/loss patterns were complex, there was also a distinct subset of tumors displaying simple karyotypic changes only. There was a statistically significant association between trisomy 7 and monosomy 10, and also between +7/-10 as putative primary aberrations and secondary losses of 1p, 9p, 13q, and 22q. The low number of tumors in the rarer histological tumor subgroups precludes definite conclusions, but there did not seem to be any clear-cut cytogenetic-pathological correlations, perhaps with the exception of ring chromosomes in giant cell glioblastomas. Our findings demonstrate that although GBM is a pathogenetically very heterogeneous group of diseases, distinct genomic aberration patterns exist.
Dahlback
Hanne-Sofie S
HS
Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. h.s.s.dahlback@medisin.uio.no
Brandal
Petter
P
Meling
Torstein R
TR
Gorunova
Ludmila
L
Scheie
David
D
Heim
Sverre
S
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018709:Statistics, Nonparametric