TY - JOUR AB - 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. AD - Department of Clinical Genetics, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, SE-41345 Gothenburg, Sweden null AU - Kryh,Hanna AU - Abrahamsson,Jonas AU - Jegerås, Elsa AU - Sjöberg,Rose-Marie AU - Devenney,Irene AU - Kogner,Per AU - Martinsson,Tommy DA - 2011/11/01 DO - 10.3892/ijo.2011.1120 EP - 1071 IS - 5 JO - Int J Oncol KW - MYCN amplification microhomology microhomology-mediated break-induced replication minimal residual disease neuroblastoma PY - 2011 SN - 1019-6439 1791-2423 SP - 1063 ST - MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma T2 - International Journal of Oncology TI - MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma UR - https://doi.org/10.3892/ijo.2011.1120 VL - 39 ER -