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J Clin Oncol. 2016 Sep 10;34(26):3195-203. doi: 10.1200/JCO.2015.66.0001. Epub 2016 Jul 18.

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.

Author information

1
Tasnim Chagtai, William Mifsud, Neil Sebire, Richard Dafydd Williams, and Kathy Pritchard-Jones, University College London Institute of Child Health, London; Sergey Popov, University Hospital of Wales; Gordan Vujanić, Cardiff University School of Medicine, Cardiff, United Kingdom; Christina Zill, Jenny Wegert, and Manfred Gessler, Wuerzburg University, Wuerzburg; Marcel Kool, German Cancer Research Center, Heidelberg; Norbert Graf, Saarland University Hospital, Homburg, Germany; Linda Dainese, Yves Le Bouc, Annick Blaise, and Aurore Coulomb, Sorbonne Universités; Linda Dainese, Yves Le Bouc, and Aurore Coulomb, Assistance Publique Hôpitaux de Paris-Hôpital Armand Trousseau, Paris; Christophe Bergeron, Centre Léon Bérard, Lyon, France; Suvi Savola, MRC-Holland; Harm van Tinteren, Netherlands Cancer Institute, Amsterdam; Godelieve A.M. Tytgat and Marry M. van den Heuvel-Eibrink, Princess Maxima Center for Pediatric Oncology/Hematology, Utrecht, the Netherlands; Peter F. Ambros and Leo Kager, Children's Cancer Research Institute; Leo Kager, St Anna Children's Hospital, Vienna, Austria; Maureen J. O'Sullivan, Our Lady's Children's Hospital, Dublin, Ireland; and Linda Holmquist Mengelbier and David Gisselsson, Lund University, Lund, Sweden.
2
Tasnim Chagtai, William Mifsud, Neil Sebire, Richard Dafydd Williams, and Kathy Pritchard-Jones, University College London Institute of Child Health, London; Sergey Popov, University Hospital of Wales; Gordan Vujanić, Cardiff University School of Medicine, Cardiff, United Kingdom; Christina Zill, Jenny Wegert, and Manfred Gessler, Wuerzburg University, Wuerzburg; Marcel Kool, German Cancer Research Center, Heidelberg; Norbert Graf, Saarland University Hospital, Homburg, Germany; Linda Dainese, Yves Le Bouc, Annick Blaise, and Aurore Coulomb, Sorbonne Universités; Linda Dainese, Yves Le Bouc, and Aurore Coulomb, Assistance Publique Hôpitaux de Paris-Hôpital Armand Trousseau, Paris; Christophe Bergeron, Centre Léon Bérard, Lyon, France; Suvi Savola, MRC-Holland; Harm van Tinteren, Netherlands Cancer Institute, Amsterdam; Godelieve A.M. Tytgat and Marry M. van den Heuvel-Eibrink, Princess Maxima Center for Pediatric Oncology/Hematology, Utrecht, the Netherlands; Peter F. Ambros and Leo Kager, Children's Cancer Research Institute; Leo Kager, St Anna Children's Hospital, Vienna, Austria; Maureen J. O'Sullivan, Our Lady's Children's Hospital, Dublin, Ireland; and Linda Holmquist Mengelbier and David Gisselsson, Lund University, Lund, Sweden. k.pritchard-jones@ucl.ac.uk.

Erratum in

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.

PMID:
27432915
PMCID:
PMC5505170
DOI:
10.1200/JCO.2015.66.0001
[Indexed for MEDLINE]
Free PMC Article

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