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The Coamplification Pattern of the MYCN Amplicon Is an Invariable Attribute of Most MYCN-Amplified Human Neuroblastomas

Authors' Affiliation: Children's Hospital, Pediatric Hematology and Oncology, University of Marburg, Marburg, Germany

Requests for reprints: Holger Christiansen, Universitaetskinderklinik, Baldinger Strasse, D-35049 Marburg, Germany. Phone: 49-6421-28-62671; Fax: 49-6421-28-66824; E-mail: holger.christiansen{at}mailer.uni-marburg.de.

Purpose: Fifteen percent to 20% of human neuroblastomas show amplification of the MYCN oncogene physiologically located at chromosome 2p24-25, indicating an aggressive subtype of human neuroblastoma with a poor clinical outcome. Recent findings revealed that the structure of the amplicon differs interindividually and that coamplification of genes in telomeric proximity to MYCN might play a relevant role in neuroblastoma development and response to treatment, respectively. We now asked if the amplicon structure is an invariable attribute of an individual tumor or if the coamplification pattern could change during progress or in case of recurrent disease.

Experimental Design: We used a previously described multiplex PCR approach to analyze the coamplification status of MYCN-amplified human neuroblastomas (n = 33) in tumor tissue at the time of initial diagnosis and in consecutive tissue specimens at later time points after initial treatment or from relapsing disease. The MYCN copy number per haploid genome (Mcn/hg) in these specimens was determined in a separate duplex PCR.

Results: In 32 of the 33 investigated tumors, the amplicon structure showed no changes after initial chemotherapy and in recurrent disease. Mcn/hg showed a decrease after initial treatment (n = 23), whereas we found a significant increase in recurrent disease (n = 10).

Conclusion: Our data indicate that the initial determined structure of the 2p24-25 amplicon is a consistent attribute in the great majority of the individual MYCN-amplified neuroblastomas and shows no plasticity during or after chemotherapy. Observed changes in the Mcn/hg over the course of disease are in line with preexisting cell culture findings.