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| 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 |
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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