Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma

  • Authors:
    • Susanne Heinsohn
    • Ulrike Evermann
    • Udo Zur Stadt
    • Stefan Bielack
    • Hartmut Kabisch
  • View Affiliations

  • Published online on: May 1, 2007     https://doi.org/10.3892/ijo.30.5.1205
  • Pages: 1205-1214
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Abstract

The retinoblastoma (RB) tumour suppressor gene is implicated in the development of several malignancies including osteosarcoma. Recent studies postulated its loss of heterozygosity (LOH) to be a poor prognostic factor at diagnosis of osteosarcoma (OS). It remains unclear whether LOH of the RB gene is suitable as a prognostic factor at diagnosis in patients with osteosarcoma. In this study we aimed to determine the early prognostic value of RB-LOH as well as the ability of denaturating high performance liquid chromatography (DHPLC) to detect LOH at this gene locus in comparison to classical PAGE. We therefore analysed 41 samples of OS on restriction fragment length polymorphisms in introns 1, 17 and 25, and variable numbers of tandem repeats (VNTRs) in intron 20. PCR fragments were separated on 1.5% agarose gel electrophoresis. VNTRs with length differentiation of only a few base pairs were analysed by 8% PAA/Spreadex gels and additionally by DHPLC. One-hundred percent concordance was observed between the results obtained by classical PAGE and DHPLC. The latter improved intron 20 analysis as a sensitive and high throughput method for detecting LOH. Overall we found 16 RB-LOH in 41 OS (39%). Three tumours exhibited additional microsatellite instability. There was no significant correlation of the event-free- and overall-survival rate or response to chemotherapy with RB-LOH found in our study. LOH positivity was associated with a significantly younger age at diagnosis. In conclusion RB-LOH could not be verified as a poor prognostic factor for osteosarcoma in the present study.

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May 2007
Volume 30 Issue 5

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

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Spandidos Publications style
Heinsohn S, Evermann U, Zur Stadt U, Bielack S and Kabisch H: Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. Int J Oncol 30: 1205-1214, 2007.
APA
Heinsohn, S., Evermann, U., Zur Stadt, U., Bielack, S., & Kabisch, H. (2007). Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. International Journal of Oncology, 30, 1205-1214. https://doi.org/10.3892/ijo.30.5.1205
MLA
Heinsohn, S., Evermann, U., Zur Stadt, U., Bielack, S., Kabisch, H."Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma". International Journal of Oncology 30.5 (2007): 1205-1214.
Chicago
Heinsohn, S., Evermann, U., Zur Stadt, U., Bielack, S., Kabisch, H."Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma". International Journal of Oncology 30, no. 5 (2007): 1205-1214. https://doi.org/10.3892/ijo.30.5.1205