Correlation between genetic alteration and long-term clinical outcome of patients with oligodendroglial tumors, with identification of a consistent region of deletion on chromosome arm 1p.
BACKGROUND
In oligodendroglial tumors, allelic losses on chromosome arms 1p and 19q are not only diagnostic molecular markers but also statistically significant predictors of both chemosensitivity and longer recurrence-free survival. In the current study, the authors attempted to analyze 21 patients genetically and clinically, with special emphasis on the correlation between genetic alterations and long-term therapeutic results.


METHODS
The authors reviewed the clinical cases of 21 patients who had undergone surgery for oligodendroglial tumors (13 oligodendrogliomas, World Health Organization [WHO] Grade II; 3 anaplastic oligodendrogliomas, WHO Grade III; 3 oligoastrocytomas, WHO Grade II; and 2 anaplastic oligoastrocytomas, WHO Grade III). Genetic testing for 1p deletions was performed using fluorescence in situ hybridization, and testing for 1p, 17p, and 19q deletions was carried out by microsatellite analysis. Survival was analyzed with univariate and multivariate Cox regression models. In addition, a high-resolution deletion map of 1p, which led to the discovery of a new deleted region on 1p, was obtained.


RESULTS
Statistical analysis revealed that both loss of 1p and loss of 19q independently and significantly predicted overall survival. A high-resolution deletion map, which displayed unusually narrow deletions, revealed a new region of deletion between D1S513 and D1S458 (1p34.3-36.11).


CONCLUSIONS
One of the putative tumor suppressor loci exists more proximally than ever reported. Based on the observation that 1p and 19q deletions predicted survival, the authors suggest further use of diagnostic and prognostic genetic testing in the clinical setting.
Hashimoto
Naoya
N
Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. nahashimoto-nsu@umin.ac.jp
Murakami
Mamoru
M
Takahashi
Yoshinobu
Y
Fujimoto
Masahito
M
Inazawa
Johji
J
Mineura
Katsuyoshi
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002648:Child; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents