Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival.
Loss of heterozygosity (LOH) on the chromosome arms 1p and 19q is frequent in oligodendroglial tumors and has been correlated with chemosensitivity and good prognosis in anaplastic oligodendrogliomas. The oligodendroglioma-associated tumor suppressor genes on 1p and 19q are as yet unknown. To narrow down candidate regions on 1p, we investigated oligodendroglial tumors from 89 patients for LOH at up to 30 polymorphic loci on 1p. In addition, all tumors were studied for LOH at 7 loci on 19q. Combined LOH on 1p and 19q was detected in 20 (83%) of 24 oligodendrogliomas, 15(63%) of 24 anaplastic oligodendrogliomas, 10 (56%) of 18 oligoastrocytomas, and 12 (52%) of 23 anaplastic oligoastrocytomas. Five tumors demonstrated partial deletions on 1p, which allowed to define 3 distinct candidate regions at 1p36.31-pter distal to D1S2633, 1p36.22-p36.31 between D1S489 and D1S2642, and 1p34.2-p36.1 between D1S2743 and D1S482, respectively. No partial deletions were detected on 19q. Combined LOH on 1p and 19q was associated with prolonged time to progression (TTP), longer overall survival (OS), and a higher 5-year survival rate. Depending on the presence or absence of combined LOH on 1p and 19q, patients with anaplastic oligodendroglial tumors treated with adjuvant radio- and/or chemotherapy showed a median TTP of 86 months versus 39 months, a median OS of 91 months versus 46 months, and a 5-year survival rate of 80% versus 36%, respectively. Similarly, LOH on 1p and 19q was associated with longer survival in patients with low-grade oligodendroglial tumors (TTP: 57 months versus 47 months; OS: 172 months versus 105 months; 5-year survival rate: 92% versus 70%). Thus, our results refine the location of putative oligodendroglioma suppressor genes on 1p and support the significance of LOH on 1p and 19q as a favorable prognostic marker.
Felsberg
Jörg
J
Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Erkwoh
Angelika
A
Sabel
Michael C
MC
Kirsch
Lutz
L
Fimmers
Rolf
R
Blaschke
Britta
B
Schlegel
Uwe
U
Schramm
Johannes
J
Wiestler
Otmar D
OD
Reifenberger
Guido
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis; D015996:Survival Rate