Linkage analysis in families with recurrent neuroblastoma

Patrizia Perri, Luca Longo, Carmel McConville, Roberto Cusano, Sally A. Rees, Marco Seri, Massimo Conte, Giovanni Romeo, Marcella Devoto, Gian Paolo Tonini

Research output: Contribution to journalArticle

Abstract

Neuroblastoma is a neural crest-derived tumor of childhood with a serious prognosis; only 20% of patients with stage 4 disease survive 5 years from diagnosis. Mechanisms involved in neuroblastoma development are unclear, but the engagement of many neuroblastoma-related gene(s) is suggested by specific chromosomal alterations. Most prominent among these is the amplification of the MYCN oncogene and the deletion of the 1p36 region. Other genetic aberrations have been discovered over the years such as deletions of 11q and 14q and gain of 17q. Although tumor aggressiveness greatly depends on the most frequent genetic abnormalities, to date no neuroblastoma-related gene has been discovered. Neuroblastoma usually occurs sporadically, but 1.5% of all diagnosed cases show familial recurrence with an autosomal dominant inheritance and incomplete penetrance. A comparison between hereditary and sporadic neuroblastomas led Knudson and Strong to gather that the two-hit hypothesis, proposed for retinoblastoma, could be applied to neuroblastoma. To determine if the 1p36 region harbors a predisposition gene for familial neuroblastoma, we carried out linkage analysis at 1p36 loci in two families with recurrent neuroblastoma. Similarly, we analyzed loci of chromosome 16, where a predisposition locus was recently mapped. We also analyzed markers located close to several candidate genes (RET, NF1, GDNF, GFRA1, EDNRB, and EDN3) involved to a different extent in other neurocristopathies. Our findings indicate that the candidate chromosomal regions and genes analyzed are not in linkage with neuroblastoma.

Original languageEnglish
Pages (from-to)74-84
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume963
Publication statusPublished - 2002

Keywords

  • 1p36 region
  • Chromosomes
  • Linkage analysis
  • MYCN oncogene
  • Neural crest cells
  • Neuroblastoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Perri, P., Longo, L., McConville, C., Cusano, R., Rees, S. A., Seri, M., Conte, M., Romeo, G., Devoto, M., & Tonini, G. P. (2002). Linkage analysis in families with recurrent neuroblastoma. Annals of the New York Academy of Sciences, 963, 74-84.