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Comprehensive analysis of chromosome 1p deletions in neuroblastoma.
Med Pediatr Oncol. 2001 Jan; 36(1):32-6.MP

Abstract

BACKGROUND

Chromosome 1p deletions are common in advanced neuroblastomas, but the biological and clinical implications of this clonal rearrangement remain controversial. Previous studies of chromosome 1p loss of heterozygosity (LOH) have been limited by analyses of relatively small number of tumors derived from heterogeneously assessed and treated patient populations. Therefore, a strictly representative cohort of 288 Children's Cancer Group neuroblastoma patients treated on the most recent phase III therapeutic trials was identified.

PROCEDURE

Primary tumors from these patients were analyzed for LOH at precisely mapped and highly informative 1p polymorphic loci located from 1p32 to 1p36.3 by multiplex PCR.

RESULTS

Ninety-three primary tumor specimens (32%) had LOH at multiple 1p36 marker loci. All 1p deletions overlapped the previously determined smallest region of overlap (SRO). One tumor had a small terminal deletion completely within 1p36.3, allowing for further refinement of the 1p36 SRO. We found no evidence to support an additional, nonoverlapping region of LOH within 1p32-36. We confirmed the strong correlation of 1p36 LOH with MYCN amplification (P < 0.001), advanced disease stage (P < 0.001), and decreased both 3-year event-free survival and overall survival probabilities (P< 0.001). When stratified for MYCN amplification status or entered into a multivariate analysis, 1p36 LOH remained predictive for decreased event-free survival, but not overall survival probability.

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.

Authors+Show Affiliations

Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104-4138, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11464900

Citation

Maris, J M., et al. "Comprehensive Analysis of Chromosome 1p Deletions in Neuroblastoma." Medical and Pediatric Oncology, vol. 36, no. 1, 2001, pp. 32-6.
Maris JM, Guo C, Blake D, et al. Comprehensive analysis of chromosome 1p deletions in neuroblastoma. Med Pediatr Oncol. 2001;36(1):32-6.
Maris, J. M., Guo, C., Blake, D., White, P. S., Hogarty, M. D., Thompson, P. M., Rajalingam, V., Gerbing, R., Stram, D. O., Matthay, K. K., Seeger, R. C., & Brodeur, G. M. (2001). Comprehensive analysis of chromosome 1p deletions in neuroblastoma. Medical and Pediatric Oncology, 36(1), 32-6.
Maris JM, et al. Comprehensive Analysis of Chromosome 1p Deletions in Neuroblastoma. Med Pediatr Oncol. 2001;36(1):32-6. PubMed PMID: 11464900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive analysis of chromosome 1p deletions in neuroblastoma. AU - Maris,J M, AU - Guo,C, AU - Blake,D, AU - White,P S, AU - Hogarty,M D, AU - Thompson,P M, AU - Rajalingam,V, AU - Gerbing,R, AU - Stram,D O, AU - Matthay,K K, AU - Seeger,R C, AU - Brodeur,G M, PY - 2001/7/24/pubmed PY - 2001/8/17/medline PY - 2001/7/24/entrez SP - 32 EP - 6 JF - Medical and pediatric oncology JO - Med Pediatr Oncol VL - 36 IS - 1 N2 - BACKGROUND: Chromosome 1p deletions are common in advanced neuroblastomas, but the biological and clinical implications of this clonal rearrangement remain controversial. Previous studies of chromosome 1p loss of heterozygosity (LOH) have been limited by analyses of relatively small number of tumors derived from heterogeneously assessed and treated patient populations. Therefore, a strictly representative cohort of 288 Children's Cancer Group neuroblastoma patients treated on the most recent phase III therapeutic trials was identified. PROCEDURE: Primary tumors from these patients were analyzed for LOH at precisely mapped and highly informative 1p polymorphic loci located from 1p32 to 1p36.3 by multiplex PCR. RESULTS: Ninety-three primary tumor specimens (32%) had LOH at multiple 1p36 marker loci. All 1p deletions overlapped the previously determined smallest region of overlap (SRO). One tumor had a small terminal deletion completely within 1p36.3, allowing for further refinement of the 1p36 SRO. We found no evidence to support an additional, nonoverlapping region of LOH within 1p32-36. We confirmed the strong correlation of 1p36 LOH with MYCN amplification (P < 0.001), advanced disease stage (P < 0.001), and decreased both 3-year event-free survival and overall survival probabilities (P< 0.001). When stratified for MYCN amplification status or entered into a multivariate analysis, 1p36 LOH remained predictive for decreased event-free survival, but not overall survival probability. 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. SN - 0098-1532 UR - https://www.unboundmedicine.com/medline/citation/11464900/Comprehensive_analysis_of_chromosome_1p_deletions_in_neuroblastoma_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0098-1532&amp;date=2001&amp;volume=36&amp;issue=1&amp;spage=32 DB - PRIME DP - Unbound Medicine ER -