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MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma
University of Gothenburg.
University of Gothenburg.
University of Gothenburg.
University of Gothenburg.
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2011 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 39, no 5, 1063-1071 p.Article in journal (Refereed) Published
Abstract [en]

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 1/10(6) 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.

Place, publisher, year, edition, pages
Spandidos Publications , 2011. Vol. 39, no 5, 1063-1071 p.
Keyword [en]
MYCN amplification, microhomology, microhomology-mediated break-induced replication, minimal residual disease, neuroblastoma
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-71544DOI: 10.3892/ijo.2011.1120ISI: 000295391600002OAI: diva2:450540
Funding Agencies|Swedish Cancer Society|09/1217 |Swedish Childrens Cancer Foundation| 07/098 |Assar Gabrielsson foundation| FB 08-86 |Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2011-10-21

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Devenney, Irene
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PediatricsFaculty of Health SciencesDepartment of Paediatrics in Linköping
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