Article Text

Download PDFPDF
Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon

Abstract

OBJECTIVES The pathological entity of primitive neuroectodermal tumour/medulloblastoma (PNET/MB) comprises a very heterogeneous group of neoplasms on a clinical as well as on a molecular level. We evaluated the importance of DNA amplification in medulloblastomas and other primitive neuroectodermal tumours (PNETs) of the CNS.

METHOD Restriction landmark genomic scanning (RLGS), a method that allows the detection of low level amplification, was used. RLGS provides direct access to DNA sequences circumventing positional cloning efforts. Furthermore, we analysed several samples by CGH.

DESIGN Twenty primary medulloblastomas, five supratentorial PNETs, and five medulloblastoma cell lines were studied.

RESULTS Although our analysis confirms that gene amplification is generally a rare event in childhood PNET/MB, we found a total of 17 DNA fragments that were amplified in seven different tumours. Cloning and sequencing of several of these fragments confirmed the previous finding ofMYC amplification in the cell line D341 Med and identified novel DNA sequences amplified in PNET/MB. We describe for the first time amplification of the novel gene,NAG, in a subset of PNET/MB. Despite genomic amplification, NAG was not overexpressed in the tumours studied. We have determined thatNAG maps less than 50 kb 5′ ofDDX1 and approximately 400 kb telomeric ofMYCN on chromosome 2p24.

CONCLUSION We found a similar but slightly higher frequency of amplification than previously reported. We present several DNA fragments that may belong to the CpG islands of novel genes amplified in a small subset of PNET/MB. As an example we describe for the first time the amplification ofNAG in the MYCNamplicon in PNET/MB.

  • medulloblastoma
  • PNET
  • NAG amplification
  • RLGS

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.