Skip to main content
SpringerLink
Log in

Genomic Profiling of Neuroblastoma Tumors – Prognostic Impact of Genomic Aberrations

  • Chapter
  • First Online:
Neuroblastoma

Part of the book series: Pediatric Cancer ((PECA,volume 1))

  • 1765 Accesses

Abstract

Neuroblastoma is a sympathetic nervous tumor that mainly affects young children. It is a very heterogeneous tumor, ranging from milder or benign forms, sometimes with the unusual ability to regress spontaneously, to lethal tumor progression despite intensive multimodal therapy. Due to the heterogeneity that neuroblastoma tumors display, it is of great importance to identify patients that need aggressive therapy and patients that will do well without aggressive therapy in order to save as many patients as possible and still minimize side-effects from the treatment. Detection of amplification of the proto-oncogene MYCN is used in risk classification protocols and recently also the deletion of chromosome 11q has been included as a prognostic factor. We have used a dense genome-wide copy number analysis with microarrays to analyze a large number of neuroblastoma tumors with the aim of improving patient stratification and reveal new features of the tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abel F, Ejeskar K, Kogner P, Martinsson T (1999) Gain of chromosome arm 17q is associated with unfavourable prognosis in neuroblastoma, but does not involve mutations in the somatostatin receptor 2(SSTR2) gene at 17q24. Br J Cancer 81(8):1402–1409

    Article  PubMed  CAS  Google Scholar 

  • Bauer A, Savelyeva L, Claas A, Praml C, Berthold F, Schwab M (2001) Smallest region of overlapping deletion in 1p36 in human neuroblastoma: a 1 Mbp cosmid and PAC contig. Genes Chromosomes Cancer 31(3):228–239

    Article  PubMed  CAS  Google Scholar 

  • Breslow N, McCann B (1971) Statistical estimation of prognosis for children with neuroblastoma. Cancer Res 31(12):2098–2103

    PubMed  CAS  Google Scholar 

  • Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3(3):203–216

    Article  PubMed  CAS  Google Scholar 

  • Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224(4653):1121–1124

    Article  PubMed  CAS  Google Scholar 

  • Brodeur GM, Sekhon G, Goldstein MN (1977) Chromosomal aberrations in human neuroblastomas. Cancer 40(5):2256–2263

    Article  PubMed  CAS  Google Scholar 

  • Carén H, Abel F, Kogner P, Martinsson T (2008a) High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem J 416(2):153–159

    Article  PubMed  Google Scholar 

  • Carén H, Erichsen J, Olsson L, Enerbäck C, Sjöberg RM, Abrahamsson J, Kogner P, Martinsson T (2008b) High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: four cases of homozygous deletions of the CDKN2A gene. BMC Genomics 9(1):353

    Article  PubMed  Google Scholar 

  • Carén H, Kryh H, Nethander M, Sjöberg RM, Träger C, Nilsson S, Abrahamsson J, Kogner P, Martinsson T (2010) High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset. Proc Natl Acad Sci USA 107:4323–4328

    Article  PubMed  Google Scholar 

  • Caron H (1995) Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma. Med Pediatr Oncol 24(4):215–221

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S (2008) Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455(7215):971–974

    Article  PubMed  CAS  Google Scholar 

  • Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D, Mosseri V, Simon T, Garaventa A, Castel V, Matthay KK (2009) The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 27(2):289–297

    Article  PubMed  Google Scholar 

  • Ejeskär K, Aburatani H, Abrahamsson J, Kogner P, Martinsson T (1998) Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene. Br J Cancer 77(11):1787–1791

    Article  PubMed  Google Scholar 

  • George RE, Sanda T, Hanna M, Frohling S, Luther W 2nd, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT (2008) Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 455(7215):975–978

    Article  PubMed  CAS  Google Scholar 

  • Gilbert F, Feder M, Balaban G, Brangman D, Lurie DK, Podolsky R, Rinaldt V, Vinikoor N, Weisband J (1984) Human neuroblastomas and abnormalities of chromosomes 1 and 17. Cancer Res 44(11):5444–5449

    PubMed  CAS  Google Scholar 

  • Guo C, White PS, Weiss MJ, Hogarty MD, Thompson PM, Stram DO, Gerbing R, Matthay KK, Seeger RC, Brodeur GM, Maris JM (1999) Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas. Oncogene 18(35):4948–4957

    Article  PubMed  CAS  Google Scholar 

  • Hallstensson K, Thulin S, Aburatani H, Hippo Y, Martinsson T (1997) Representational difference analysis and loss of heterozygosity studies detect 3p deletions in neuroblastoma. Eur J Cancer 33(12):1966–1970

    Article  PubMed  CAS  Google Scholar 

  • Janoueix-Lerosey I, Lequin D, Brugieres L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Puisieux A, Schleiermacher G, Pierron G, Valteau-Couanet D, Frebourg T, Michon J, Lyonnet S, Amiel J, Delattre O (2008) Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 455(7215):967–970

    Article  PubMed  CAS  Google Scholar 

  • Li R, Morris SW (2008) Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Med Res Rev 28(3):372–412

    Article  PubMed  CAS  Google Scholar 

  • Martinsson T, Sjöberg R-M, Hedborg F, Kogner P (1995) Deletion of chromosome 1p loci and microsatellite instability in neuroblastomas analyzed with short-tandem repeat polymorphisms. Cancer Res 55(23):5681–5686

    PubMed  CAS  Google Scholar 

  • Mosse YP, Greshock J, Margolin A, Naylor T, Cole K, Khazi D, Hii G, Winter C, Shahzad S, Asziz MU, Biegel JA, Weber BL, Maris JM (2005) High-resolution detection and mapping of genomic DNA alterations in neuroblastoma. Genes Chromosomes Cancer 43(4):390–403

    Article  PubMed  CAS  Google Scholar 

  • Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM (2008) Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 455(7215):930–935

    Google Scholar 

  • Nannya Y, Sanada M, Nakazaki K, Hosoya N, Wang L, Hangaishi A, Kurokawa M, Chiba S, Bailey DK, Kennedy GC, Ogawa S (2005) A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays. Cancer Res 65(14):6071–6079

    Article  PubMed  CAS  Google Scholar 

  • Savelyeva L, Corvi R, Schwab M (1994) Translocation involving 1p and 17q is a recurrent genetic alteration of human neuroblastoma cells. Am J Hum Genet 55(2):334–340

    PubMed  CAS  Google Scholar 

  • Schleiermacher G, Raynal V, Janoueix-Lerosey I, Combaret V, Aurias A, Delattre O (2004) Variety and complexity of chromosome 17 translocations in neuroblastoma. Genes Chromosomes Cancer 39(2):143–150

    Article  PubMed  CAS  Google Scholar 

  • Schwab M, Alitalo K, Klempnauer KH, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J (1983) Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 305(5931):245–248

    Article  PubMed  CAS  Google Scholar 

  • Srivatsan ES, Ying KL, Seeger RC (1993) Deletion of chromosome 11 and of 14q sequences in neuroblastoma. Genes Chromosomes Cancer 7(1):32–37

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Yokota J, Mugishima H, Okabe I, Ookuni M, Sugimura T, Terada M (1989) Frequent loss of heterozygosity on chromosome 14q in neuroblastoma. Cancer Res 49(5):1095–1098

    PubMed  CAS  Google Scholar 

  • Thompson PM, Seifried BA, Kyemba SK, Jensen SJ, Guo C, Maris JM, Brodeur GM, Stram DO, Seeger RC, Gerbing R, Matthay KK, Matise TC, White PS (2001) Loss of heterozygosity for chromosome 14q in neuroblastoma. Med Pediatr Oncol 36(1):28–31

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto G, Nannya Y, Kato M, Sanada M, Levine RL, Kawamata N, Hangaishi A, Kurokawa M, Chiba S, Gilliland DG, Koeffler HP, Ogawa S (2007) Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays. Am J Hum Genet 81(1):114–126

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UCL Cancer Institute, University College London, London, WC1E 6BT, UK

    Helena Carén

Authors
  1. Helena Carén
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helena Carén .

Editor information

Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Carén, H. (2012). Genomic Profiling of Neuroblastoma Tumors – Prognostic Impact of Genomic Aberrations. In: Hayat, M. (eds) Neuroblastoma. Pediatric Cancer, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2418-1_21

Download citation

Publish with us

Policies and ethics

Search

Navigation