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Lookup NU author(s): Dr Nicholas Bown, Julie Freeman-Edward, Professor John LunecORCiD, Dr Katia Mazzocco, Steven O'Neill, Professor Andrew Pearson
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Purpose : Therapy stratification based on genetic markers is becoming increasingly important, which makes commitment to the highest possible reliability of the involved markers mandatory. In neuroblastic tumors, amplification of the MYCN gene is an unequivocal marker that indicates aggressive tumor behavior and is consequently used for therapy stratification. To guarantee reliable and standardized quality of genetic features, a quality-assessment study was initiated by the European Neuroblastoma Quality Assessment (ENQUA; connected to International Society of Pediatric Oncology) Group. Materials and Methods: One hundred thirty-seven coded specimens from 17 tumors were analyzed in 11 European national/regional reference laboratories using molecular techniques, in situ hybridization, and flow and image cytometry. Tumor samples with divergent results were re-evaluated. Results: Three hundred fifty-two investigations were performed, which resulted in 23 divergent findings, 17 of which were judged as errors after re-evaluation. MYCN analyses determined by Southern blot and in situ hybridization led to 3.7% and 4% of errors, respectively. Tumor cell content was not indicated in 32% of the samples, and 11% of seemingly correct MYCN results were based on the investigation of normal cells (eg, Schwann cells). Thirty-eight investigations were considered nonassessable. Conclusion: This study demonstrated the importance of revealing the difficulties and limitations for each technique and problems in interpreting results, which are crucial for therapeutic decisions. Moreover, it led to the formulation of guidelines that are applicable to all kinds of tumors and that contain the standardization of techniques, including the exact determination of the tumor cell content. Finally, the group has developed a common terminology for molecular-genetic results. (C) 2003 by American Society of Clinical Oncology.
Author(s): Ambros, I.M., Benard, J., Boavida, M., Bown, N., Caron, H., Combaret, V., Couturier, J., Darnfors, C., Delattre, O., Freeman-Edward, J., Gambini, C., Gross, N., Hattinger, C.M., Luegmayr, A., Lunec, J., Martinsson, T., Mazzocco, K., Navarro, S., Noguera, R., O'Neill, S., Potschger, U., Rumpler, S., Speleman, F., Tonini, G.P., Valent, A., Van Roy, N., Amann, G., De Bernardi, B., Kogner, P., Ladenstein, R, Mickon, J., Pearson, A.D.J., Ambros, P.F.
Publication type: Article
Publication status: Unknown
Journal: Journal of Clinical Oncology
Year: 2003
Volume: 21
Issue: 11
Pages: 2077-2084
ISSN (print): 0732-183X
ISSN (electronic): 1527-7755
URL: http://dx.doi.org/10.1200/JCO.2003.03.025
DOI: 10.1200/JCO.2003.03.025
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