Journal Article

DKFZ-2017-01742

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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, T. ; Zill, C. ; Dainese, L. ; Wegert, J. ; Savola, S. ; Popov, S. ; Mifsud, W. ; Vujanić, G. ; Sebire, N. ; Le Bouc, Y. ; Ambros, P. F. ; Kager, L. ; O'Sullivan, M. J. ; Blaise, A. ; Bergeron, C. ; Mengelbier, L. H. ; Gisselsson, D. ; Kool, M.DKFZ* ; Tytgat, G. A. M. ; van den Heuvel-Eibrink, M. M. ; Graf, N. ; van Tinteren, H. ; Coulomb, A. ; Gessler, M. ; Williams, R. D. ; Pritchard-Jones, K.

2016
American Society of Clinical Oncology Alexandria, Va.

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Please use a persistent id in citations: doi:10.1200/JCO.2015.66.0001

Abstract: 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.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.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.Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.

Keyword(s): Biomarkers, Tumor

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2016

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Database coverage:
; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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