Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors.
To narrow down the putative tumor-suppressor gene locus and to assess the predictability of clinical courses by genomic alterations, we analyzed 46 oligodendroglial tumors for loss of heterozygosity (LOH) in the distal region of the short arm of chromosome 1. LOH at 1p was found in 43 tumors (93.5%), including all 28 oligodendrogliomas, all eight oligo-astrocytomas, six of eight anaplastic oligodendrogliomas, and in one of two anaplastic oligo-astrocytomas. Thirty-seven tumors showed LOH patterns consistent with a large terminal deletion, whereas six tumors showed LOH suggesting interstitial deletions. Our data also showed two small regions of overlap at 1p34-p35 (approximately 5.7 Mb) and at 1p36.1-p36.2 ( approximately 12 Mb). Among the six tumors with interstitial deletion, the proximal region was deleted in five tumors, whereas the distal region was deleted in only half of them. Overall, 91% of tumors showed deletion including this proximal region. To examine the clinical significance of the LOH pattern, the samples were classified into three groups: tumors without 1p LOH (Group 1, n = 3), tumors with an interstitial deletion (Group 2, n = 6), and tumors with a large terminal deletion (Group 3, n = 37). Both overall and progression-free survival of patients in Group 2 was extremely poor compared with those included in Group 3 (P = 0.0006 and P = 0.003, respectively). As to the clinical response to chemotherapy, nimustine prevented tumor recurrence in Group 3 (P = 0.034) but not in Group 2. Our results demonstrate that a putative tumor-suppressor gene(s) in oligodendroglial tumors is localized at 1p34-p35 and that small interstitial deletions, in contrast to large terminal deletions, are strongly predictive of both chemoresistance and aggressive characteristics of these tumors.
Iuchi
Toshihiko
T
Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan. tiuchi@chiba-cc.pref.chiba.jp
Namba
Hiroki
H
Iwadate
Yasuo
Y
Shishikura
Tomotane
T
Kageyama
Hajime
H
Nakamura
Yoko
Y
Ohira
Miki
M
Yamaura
Akira
A
Osato
Katsunobu
K
Sakiyama
Shigeru
S
Nakagawara
Akira
A
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D011379:Prognosis; D015996:Survival Rate / Q000639:trends