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Cancers 2013, 5(2), 662-675; doi:10.3390/cancers5020662

Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse

Laboratoire de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098, France
EA4438, Groupe Marqueurs Moléculaires de Progression Tumorale et de Sensibilisation aux Drogues Anti-Cancéreuses, University of Strasbourg, 3 Avenue Molière, Strasbourg 67000, France
Laboratoire d'Anatomie Pathologique, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098, France
Service de Pédiatrie Onco-Hématologie, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098, France
Author to whom correspondence should be addressed.
Received: 13 March 2013 / Revised: 5 April 2013 / Accepted: 22 April 2013 / Published: 4 June 2013
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Currently, the treatment of pediatric high-grade osteosarcomas systematically includes one topoisomerase IIα inhibitor. This chemotherapy is usually adapted to the response to the neo-adjuvant therapy after surgery. The current and unique marker of chemoresponsiveness is the percentage of viable residual cells in the surgical resection. This late patient management marker has to be evaluated earlier in the therapeutic history of the patients on initial biopsy. Therefore, new biomarkers, especially those involved in the topoisomerase IIα inhibitor response might be good candidates. Therefore, our study was designed to target TOP1, TOP2A and TOP2B genes in 105 fresh-frozen diagnostic biopsies by allelotyping and real-time quantitative PCR. Our analyses in those pediatric osteosarcomas, homogeneously treated, highlighted the frequent involvement of topo-isomerase genes. The main and most important observation was the statistical link between the presence of TOP2A amplification and the good response to neo-adjuvant chemotherapy. Compared to adult cancers, the 17q21 amplicon, including TOP2A and ERBB2 genes, seems to be differentially implicated in the osteosarcoma chemoresponsiveness. Surprisingly, there is no ERBB2 gene co-amplification and the patients harboring TOP2A amplification tend to show a worse survival, so TOP2A analyses remain a preliminary, but a good molecular approach for the evaluation at diagnosis of pediatric osteosarcoma chemoresponsiveness.
Keywords: topoisomerase; osteosarcoma; chemoresponse topoisomerase; osteosarcoma; chemoresponse
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Nguyen, A.; Lasthaus, C.; Guerin, E.; Marcellin, L.; Pencreach, E.; Gaub, M.-P.; Guenot, D.; Entz-Werle, N. Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse. Cancers 2013, 5, 662-675.

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