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MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma.

Journal article
Authors Hanna Kryh
Jonas Abrahamsson
Elsa Jegerås
Rose-Marie Sjöberg
Irene Devenney
Per Kogner
Tommy Martinsson
Published in International journal of oncology
Volume 39
Issue 5
Pages 1063-71
ISSN 1791-2423
Publication year 2011
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Institute of Clinical Sciences, Department of Pediatrics
Pages 1063-71
Language en
Links dx.doi.org/10.3892/ijo.2011.1120
Subject categories Neurobiology, Cancer and Oncology

Abstract

The MYCN gene is frequently amplified in unfavorable neuroblastoma tumors. Therefore, this study aimed at characterizing the novel junctions connecting the amplified DNA segments (amplicons) and obtaining tumor-specific PCR fragments for use in detecting minimal residual disease (MRD). High-density SNP arrays were used to map the end-points of the MYCN amplicons in a subset of neuroblastoma tumors. Primers were designed to give rise to a tumor-specific PCR product and were examined for MRD in the blood and bone marrow using quantitative PCR. Tumor-specific junction fragments were detected in all cases, confirming a head-to-tail tandem orientation of the amplicons and revealing microhomology at the amplicon junctions, thus suggesting a rolling circle caused by microhomology-mediated break-induced replication (MMBIR) as a possible mechanism initiating the MYCN amplification. We also evaluated the use of these junctions as tumor-specific targets for detecting MRD and observed that tumor DNA could be readily detected and quantified in either blood or bone marrow at a sensitivity of 1/106 tumor/control DNA. This study provides new information on the mechanisms of oncogene amplification and envisages means of rapidly obtaining highly sensitive PCR-based tools for tumor/patient-specific monitoring of treatment response and the early detection of relapse in patients with neuroblastoma.

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