PMID- 12764740 OWN - NLM STAT- MEDLINE DCOM- 20030627 LR - 20161124 IS - 0098-1532 (Print) IS - 0098-1532 (Linking) VI - 41 IP - 1 DP - 2003 Jul TI - FISH analyses for alterations in chromosomes 1, 2, 3, and 11 define high-risk groups in neuroblastoma. PG - 30-5 AB - BACKGROUND: The prognostic chromosomal markers 1p loss and MYCN amplification (MNA) are only present in a subgroup of approximately 30% of neuroblastomas. To further characterize high and low risk subsets we investigated alterations in chromosome arms 3p and 11q, additional changes in 1p and MYCN as well as the somy-status of chromosome 1 in the same sample. PROCEDURE: Fluorescence in situ hybridization (FISH) was used as an alternative technique to PCR/LOH- or comparative genomic hybridization (CGH) analyses. Alterations in chromosomes 3p and 11q were investigated in 182 unselected tumors, 1p loss and MNA in 174 and 179 of these, respectively. The somy-status of chromosome 1 was determined in 165 tumors as it highly correlates with the tumor ploidy. RESULTS: Alterations in the four chromosomal regions were found in the following frequencies: 3p26: 19%, 11q23: 29%, 1p36: 29%, MNA: 19%. Fifty-two percent of all cases displayed structural aberrations in at least one chromosomal region, 83% in stage 4 and 30% in stages 1-3, 4s. All aberrations were thus correlated with stage 4 disease but were also present in a substantial subset of localized and 4s tumors. Trisomy of chromosome 1 was found in 38% of the tumors, disomy or tetrasomy in 62%. Patients with alterations in any of the four chromosomes and di/tetrasomy 1 showed a significantly increased age at diagnosis. Loss in 1p and MNA were closely associated with each other, as well as 3p and 11q aberrations but not the groups 1p/MNA versus 3p/11q. Only a small portion of trisomic tumors showed aberrations in at least one of the four chromosomal regions (14%) in contrast to the majority of the di/tetrasomic cases (74%). As already known the MYCN status discriminated between good and poor outcome in localized and metastatic stage 4 tumors. In addition alterations in 1p or 11q, deletion in 3p and di/tetrasomy 1 were associated with an unfavorable prognosis in MYCN single copy tumors of stages 1-3, 4s. Multivariate analysis revealed 11q alterations and MNA as the most important chromosomal prognostic factors in all stages. CONCLUSION: FISH analyses for chromosomal alterations in 3p and 11q as well as in 1p and MYCN allows to define different groups with an increased risk for disease progression. CI - Copyright 2003 Wiley-Liss, Inc. FAU - Spitz, Ruediger AU - Spitz R AD - University Children's Hospital, Pediatric Oncology, Koln, Germany. Ruedinger.Spitz@medizin.uni-koeln.de FAU - Hero, Barbara AU - Hero B FAU - Ernestus, Karen AU - Ernestus K FAU - Berthold, Frank AU - Berthold F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Med Pediatr Oncol JT - Medical and pediatric oncology JID - 7506654 RN - 0 (DNA Probes) RN - 0 (MYCN protein, human) RN - 0 (N-Myc Proto-Oncogene Protein) RN - 0 (Nuclear Proteins) RN - 0 (Oncogene Proteins) SB - IM MH - Child MH - *Chromosome Deletion MH - Chromosomes, Human/*genetics MH - Chromosomes, Human, Pair 1/genetics MH - Chromosomes, Human, Pair 11/genetics MH - Chromosomes, Human, Pair 2/genetics MH - Chromosomes, Human, Pair 3/genetics MH - Cohort Studies MH - DNA Probes MH - Female MH - Germany MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - N-Myc Proto-Oncogene Protein MH - Neoplasm Recurrence, Local/diagnosis MH - Neoplasm Staging MH - Neuroblastoma/*diagnosis/genetics/mortality/pathology MH - Nuclear Proteins/*genetics MH - Oncogene Proteins/*genetics MH - Proportional Hazards Models MH - Survival Analysis EDAT- 2003/05/24 05:00 MHDA- 2003/06/28 05:00 CRDT- 2003/05/24 05:00 PHST- 2003/05/24 05:00 [pubmed] PHST- 2003/06/28 05:00 [medline] PHST- 2003/05/24 05:00 [entrez] AID - 10.1002/mpo.10313 [doi] PST - ppublish SO - Med Pediatr Oncol. 2003 Jul;41(1):30-5. doi: 10.1002/mpo.10313.