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Weak linkage at 4p16 to predisposition for human neuroblastoma

Oncogene volume 21, pages 8356–8360 (2002)Cite this article

Abstract

The most frequent genetic alterations described in neuroblastoma (NB) are amplification of MYCN oncogene and deletion of chromosome 1p, although somatic deletions have been demonstrated at other chromosomal intervals. Since loss of heterozygosity (LOH) at distal 4p has been observed in about 20–29% of neuroblastomas, we have evaluated deletions in 41 Italian NB samples by LOH analysis at loci mapping to 4p as follows: pter-D4S2936-D4S412-D4S2957-D4S432-D4S3023-D4S431-cen. Our analysis showed allele losses in eight out of 41 samples (19.5%) and allowed the identification of a smallest region of overlapping deletion (SRO) of 3.0 cM, delimited by D4S412 and D4S3023. Two of these tumors with 4p LOH are from patients belonging to a family with recurrent NB. Interestingly the genotyping of this family revealed an identical haplotype that includes the nonrecombinant loci D4S412, D4S2957 and D4S432 shared by all affected children and demonstrated that this haplotype is retained in the two tumors carrying somatic deletions from patients of this family. Furthermore linkage analysis was performed in two NB families and yielded an overall lod-score of 3.0 in the interval including the haplotype. This provides a confirmatory indication that the region delimited by D4S2936 and D4S3023, which also includes the new defined SRO, may harbor NB predisposing gene/s.

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Acknowledgements

This work was supported by Fondazione Italiana per la Lotta al Neuroblastoma. We are grateful to surgeons, clinicians and pathologists of the Italian Cooperative Group for Neuroblastoma and AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) supplying tumor samples and clinical data, to Dr Katia Mazzocco for MYCN amplification and 1p deletion data and to Dr Roberta Bricchetto for language revision.

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Author notes

  1. Patrizia Perri and Luca Longo: Authors have equally contributed to the present work

Authors and Affiliations

  1. Laboratory of Neuroblastoma Research, Advanced Biotechnology Center, Genoa, 16132, Italy

    Patrizia Perri

  2. Laboratory of Population Genetics, National Institute for Cancer Research (IST), Genoa, 16132, Italy

    Patrizia Perri, Luca Longo & Gian Paolo Tonini

  3. Laboratory of Molecular Genetics, Gaslini Children's Hospital, Genoa, 16148, Italy

    Roberto Cusano & Marco Seri

  4. Department of Paediatrics and Child Health, University of Birmingham, Birmingham B15 2TT, UK

    Carmel M McConville & Sally A Rees

  5. Department of Oncology, Biology and Genetics, University of Genoa, Genoa, 16132, Italy

    Marcella Devoto

  6. Department of Research, AI duPont Hospital for Children, Wilmington, 19899, Delaware, DE, USA

    Marcella Devoto

  7. Department of Hematology and Oncology, Gaslini Children's Hospital, Genoa, 16148, Italy

    Massimo Conte

  8. Laboratory of Immunogenetics, National Institute for Cancer Research (IST), Genoa, 16132, Italy

    Giovanni Battista Ferrara

  9. Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, 40138, Italy

    Marco Seri & Giovanni Romeo

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  1. Patrizia Perri
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  2. Luca Longo
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  11. Gian Paolo Tonini
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Corresponding author

Correspondence to Gian Paolo Tonini.

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Perri, P., Longo, L., Cusano, R. et al. Weak linkage at 4p16 to predisposition for human neuroblastoma. Oncogene 21, 8356–8360 (2002). https://doi.org/10.1038/sj.onc.1206009

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