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Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas

Oncogene volume 18, pages 4948–4957 (1999)Cite this article

Abstract

Deletions of the long arm of chromosome 11 (11q) have been noted in primary neuroblastomas, but a comprehensive analysis has not been performed. Therefore, we analysed 331 neuroblastomas (295 sporadic, 15 familial and 21 tumor-derived cell lines) to determine the prevalence of 11q allelic deletions, to map the location of a putative tumor suppressor gene and to perform clinical correlative studies. Assays for loss of heterozygosity (LOH) were performed at 24 microsatellite loci spanning 11q. LOH was observed at multiple 11q loci in 129/295 (44%) sporadic neuroblastomas, 5/15 (33%) familial neuroblastomas, and 5/21 (24%) neuroblastoma cell lines. A single region of 2.1 cM within 11q23.3, flanked by markers D11S1340 and D11S1299, was deleted in all specimens with 11q LOH. Allelic loss at 11q23 was inversely related to MYCN amplification (P<0.001). Within the subset of cases with a single copy of MYCN, 11q LOH was associated with advanced stage disease (P=0.008), unfavorable histopathology (P=0.042), and decreased overall survival probability (P=0.008). However, 11q LOH was not independently prognostic in multivariate analyses. These data support the hypothesis that a tumor suppressor gene mapping within 11q23.3 is commonly inactivated during the malignant evolution of a large subset of neuroblastomas, especially those with unamplified MYCN.

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Acknowledgements

The authors would like to thank the member institutions of the CCG for providing patient samples, Mr Richard Gallego for specimen processing, Mr David Blake for technical assistance and Dr CP Reynolds for providing some of the neuroblastoma cell lines. This work was supported by grants from the National Institutes of Health CA-13539 (Children's Cancer Group), CA-78545 and CA-78966 (JM Maris), CA-39771 (GM Brodeur), CA-60104 (RC Seeger), by funds provided through the Audrey E Evans Endowed Chair at the Children's Hospital of Philadelphia (GM Brodeur) and by Career Development Awards through the American Society of Clinical Oncology (JM Maris) and the American Cancer Society (JM Maris).

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Authors and Affiliations

  1. Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, Pennsylvania, USA

    Chun Guo, Peter S White, Matthew J Weiss, Michael D Hogarty, Patricia M Thompson, Garrett M Brodeur & John M Maris

  2. Department of Pediatrics, University of Pennsylvania School of Medicine, PA 19104, Philadelphia, USA

    Garrett M Brodeur & John M Maris

  3. Children's Cancer Group, Arcadia, CA 91066, California, USA

    Peter S White, Michael D Hogarty, Daniel O Stram, Robert Gerbing, Katherine K Matthay, Robert C Seeger, Garrett M Brodeur & John M Maris

  4. Department of Pediatrics, University of Southern California School of Medicine, Los Angeles, CA 90027, California, USA

    Daniel O Stram & Robert C Seeger

  5. Department of Pediatrics, University of California at San Francisco School of Medicine, San Francisco, CA 94143, California, USA

    Katherine K Matthay

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  1. Chun Guo
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Guo, C., White, P., Weiss, M. et al. Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas. Oncogene 18, 4948–4957 (1999). https://doi.org/10.1038/sj.onc.1202887

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