Comprehensive analysis of chromosome 1p deletions in neuroblastoma

Citation
Jm. Maris et al., Comprehensive analysis of chromosome 1p deletions in neuroblastoma, MED PED ONC, 36(1), 2001, pp. 32-36
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pediatrics
Journal title
MEDICAL AND PEDIATRIC ONCOLOGY
ISSN journal
0098-1532 → ACNP
Volume
36
Issue
1
Year of publication
2001
Pages
32 - 36
Database
ISI
SICI code
0098-1532(200101)36:1<32:CAOC1D>2.0.ZU;2-3
Abstract
Background. Chromosome Ip deletions are common in advanced neuroblastomas, but the biological and clinical implications of this clonal rearrangement r emain controversial. Previous studies of chromosome 1p loss of heterozygosi ty (LOH) have been limited by analyses of relatively small number of tumors derived from heterogeneously assessed and treated patient populations. The refore, a strictly representative cohort of 288 Children's Cancer Group neu roblastoma patients treated on the most recent phase III therapeutic trials was identified. Procedure. Primary tumors from these patients were analyze d for LOH at precisely mapped and highly informative Ip polymorphic loci lo cated from 1p32 to 1p36.3 by multiplex PCR. Results, Ninety-three primary t umor specimens (32%) had LOH at multiple 1p36 marker loci. All Ip deletions overlapped the previously determined smallest region of overlap (SRO). One tumor had a small terminal deletion completely within 1p36.31 allowing for further refinement of the 1p36 SRO. We found no evidence to support an add itional, nonoverlapping region of LOH within 1p32-36. We confirmed the stro ng correlation of 1p36 LOH with MYCN amplification (P < 0.001), advanced di sease stage (P < 0.001), and decreased both 3-year event-free survival and overall survival probabilities (P < 0.001). When stratified for MYCN amplif ication status or entered into a multivariate analysis, 1p36 LOH remained p redictive for decreased event-free survival, but not overall survival proba bility. Conclusions. These data support the hypothesis that inactivation of a tumor suppressor gene within 1p36.3 is associated with an increased risk for disease relapse. Med. Pediatr. Oncol. 36.32-36, 2001. (C) 2001 Wiley-L iss. Inc.