Comprehensive analysis of the 9p21 region in neuroblastoma suggests a role for genes mapping to 9p21-23 in the biology of favourable stage 4 tumours

J. Mora, M. Alaminos, C. De Torres, Peter B Illei, J. Qin, N. K V Cheung, W. L. Gerald

Research output: Contribution to journalArticle

Abstract

Chromosome 9p21 is frequently deleted in many cancers. Previous reports have indicated that 9p21 LOH is an uncommon finding in neuroblastoma (NB), a tumour of childhood. We have performed an extensive analysis of 9p21 and genes located in this region (cyclin-dependent kinase inhibitor 2A - CDKN2A/p16 INK4a, CDKN2A/p14ARF, CDKN2B/p15INK4b, MTAP, interferon α and β cluster). LOH was detected in 16.4% of 177 NB. The SRO was identified between markers D9S1751 and D9S254, at 9p21-23, a region telomeric to the CDKN2/A and MTAP genes. A significantly better overall and progression-free survival was detected in stage 4 patients displaying 9p21-23 LOH. Hemizygous deletion of the region harbouring the CDKN2A and CDKN2B loci was identified in two tumours by means of fluorescent in situ hybridisation and MTAP was present by immunostaining in all but one tumour analysed. The transcriptional profile of tumours with 9p21-23 LOH was compared to that of NB displaying normal 9p21-23 status by means of oligonucleotide microarrays. Four of the 363 probe sets downregulated in tumours with 9p21-23 LOH were encoded by genes mapping to 9p22-24. The only well-characterised transcript among them was nuclear factor 1-B3. Our results suggest a role for genes located telomeric of 9p21 in good risk NB.

Original languageEnglish (US)
Pages (from-to)1112-1118
Number of pages7
JournalBritish Journal of Cancer
Volume91
Issue number6
DOIs
Publication statusPublished - Sep 13 2004
Externally publishedYes

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Keywords

  • CDKN2A
  • Microarrays
  • MTAP
  • Neuroblastoma
  • Nuclear factor 1-B3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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