gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

The Structure of the MYCN Amplicon is an Invariable Attribute in Human Neuroblastoma

Meeting Abstract

  • corresponding author presenting/speaker Axel Weber - Pädiatrische Onkologie, Zentrum für Kinder- und Jugendmedizin der Philipps-Universität Marburg, Universitätsklinikum Gießen und Marburg, Deutschland
  • Sven Starke - Pädiatrische Onkologie, Zentrum für Kinder- und Jugendmedizin der Philipps-Universität Marburg, Universitätsklinikum Gießen und Marburg
  • Eckhard Bergmann - Pädiatrische Onkologie, Zentrum für Kinder- und Jugendmedizin der Philipps-Universität Marburg, Universitätsklinikum Gießen und Marburg
  • Holger Christiansen - Pädiatrische Onkologie, Zentrum für Kinder- und Jugendmedizin der Philipps-Universität Marburg, Universitätsklinikum Gießen und Marburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO628

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk736.shtml

Veröffentlicht: 20. März 2006

© 2006 Weber et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Purpose: 15% to 20% of human neuroblastoma show amplification of the MYCN oncogene at chromosome 2p24-25. Amplification of MYCN identifies an aggressive subtype of human neuroblastoma with a poor clinical outcome. The median incidence of MYCN amplified tumors is thereby strongly related to a definite age at dignosis of 18-24 months. Recently we and others could show that the structure of the amplicon differes from patient to patient and that coamplification of genes in telomeric proximity to MYCN might play a relevant role for neuroblastoma pathogenesis and clinical prognosis. We now asked wether the amplicon structure is an invariable attribute of the individual tumor or if the amplicon structure could change during progress or in case of a recurrent disease.

Patients and Methods: We used a previously described multiplex PCR approach to analyse the coamplification status of n=33 MYCN amplified human neuroblastomas for the tumor tissue at time of initial diagnosis and in consecutive tissue probes at later time points of progressive disease or for tissue probes of recurrent disease.

Results: In 32 of the 33 investigated tumors the amplicon structure showed no changes after initial chemotherapy and in recurrend disease respectively. However, in one single patient we found genes, that had been identified as coamplified at the time of initial diagnosis not to be coamplified at later time points of recurrent disease.

Conclusion: Our data indicate, that the initial determined structure of the 2p24-25 amplicon is a definite attribute of the invdividual tumor in the great majority of cases and shows no plasticity during or after therapy with DNA interacting agents. Thus, the amplicon structure does not change during disease progression or in recurrency. However, changes in the structure of the amplicon and / or selection of subclones of neuroblastoma cells during therapy with a different amplification pattern compared to that one of the initially predominant clones, seem to be possible events in neuroblastoma disease.