Open Access

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

  • Authors:
    • Hanna Kryh
    • Jonas Abrahamsson
    • Elsa Jegerås
    • Rose-Marie Sjöberg
    • Irene Devenney
    • Per Kogner
    • Tommy Martinsson
  • View Affiliations

  • Published online on: July 12, 2011     https://doi.org/10.3892/ijo.2011.1120
  • Pages: 1063-1071
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

November 2011
Volume 39 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Kryh, H., Abrahamsson, J., Jegerås, ., Sjöberg, R., Devenney, I., Kogner, P., & Martinsson, T. (2011). MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma. International Journal of Oncology, 39, 1063-1071. https://doi.org/10.3892/ijo.2011.1120
MLA
Kryh, H., Abrahamsson, J., Jegerås, ., Sjöberg, R., Devenney, I., Kogner, P., Martinsson, T."MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma". International Journal of Oncology 39.5 (2011): 1063-1071.
Chicago
Kryh, H., Abrahamsson, J., Jegerås, ., Sjöberg, R., Devenney, I., Kogner, P., Martinsson, T."MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma". International Journal of Oncology 39, no. 5 (2011): 1063-1071. https://doi.org/10.3892/ijo.2011.1120