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Gain of 1q as a prognostic biomarker in Wilms Tumors (WTs) treated with preoperative chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 trial: a SIOP renal tumours biology consortium study

Chagtai, Tasnim, Zill, Christina, Dainese, Linda, Wegert, Jenny, Savola, Suvi, Popov, Sergey, Mifsud, William, Vujanic, Gordan, Sebire, Neil, Le Bouc, Yves, Ambros, Peter F., Kager, Leo, O'Sullivan, Maureen J., Blaise, Annick, Bergeron, Christophe, Mengelbier, Linda Holmquist, Gisselsson, David, Kool, Marcel, Tytgat, Godelieve A.M., van den Heuvel-Eibrink, Marry M., Graf, Norbert, van Tinteren, Harm, Coulomb, Aurore, Gessler, Manfred, Williams, Richard Dafydd and Pritchard-Jones, Kathy 2016. Gain of 1q as a prognostic biomarker in Wilms Tumors (WTs) treated with preoperative chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 trial: a SIOP renal tumours biology consortium study. Journal of Clinical Oncology 34 (26) , pp. 3195-3203. 10.1200/JCO.2015.66.0001

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Abstract

Purpose Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P < .001; hazard ratio, 2.33) and OS (P = .01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Licensed under the Creative Commons Attribution 4.0 License.
Publisher: American Society of Clinical Oncology
ISSN: 0732-183X
Date of First Compliant Deposit: 14 November 2019
Last Modified: 14 Nov 2019 15:30
URI: http://orca.cf.ac.uk/id/eprint/103143

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