Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors.
Deletions on chromosomes 1p and 19q are associated with favorable prognosis in patients with oligodendroglial tumors. The aim of our study was to identify additional genomic aberrations linked to patient survival. We performed a genome-wide screen for genomic imbalances by comparative genomic hybridization on tumors from 70 patients, including 40 oligodendrogliomas, 30 oligoastrocytomas (21 WHO grade II tumors, 49 WHO grade III tumors). Data were correlated with overall patient survival (OS, median follow-up: 5.8 years). The most frequent aberrations were losses on chromosome 19q (64%), 1p (59%), 9p (26%), 4q (21%), 10q (19%), 18q (17%); gains on 7q (24%), 19p (19%), 7p (17%). In univariate analyses, combined 1p/19q and 19q loss were significantly associated with longer OS, and gains on 7, 8q, 19q, 20, losses on 9p, 10, 18q, Xp with shorter OS. Multivariate analyses showed the most significant prognostic factors for OS of patients with any oligodendroglial tumor to be WHO grade [odds ratio (OR) 8], 7p gain (OR 6), 9p loss (OR 3); for OS of patients with anaplastic tumors to be 7p gain (OR 10), 8q gain (OR 5), 18q loss (OR 3). Patients with anaplastic oligodendroglial tumors containing one or more prognostically unfavorable genomic aberration had a poor outcome independent of the 1p/19q status. In summary, we identified several independent genomic markers of shorter survival in patients with oligodendroglial tumors. Thus, molecular diagnostic testing, which is usually restricted to 1p/19q deletion analysis, may need to be refined by additionally assessing the prognostically unfavorable genomic aberrations identified.
Trost
Detlef
D
Department of Human Genetics, Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
Ehrler
Marion
M
Fimmers
Rolf
R
Felsberg
Jörg
J
Sabel
Michael C
MC
Kirsch
Lutz
L
Schramm
Johannes
J
Wiestler
Otmar D
OD
Reifenberger
Guido
G
Weber
Ruthild G
RG
D000293:Adolescent; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate