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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Tasnim Chagtai
  • Christina Zill
  • Linda Dainese
  • Jenny Wegert
  • Suvi Savola
  • Sergey Popov
  • William Mifsud
  • Gordan Vujanić
  • Neil Sebire
  • Yves Le Bouc
  • Peter F. Ambros
  • Leo Kager
  • Maureen J. O'Sullivan
  • Annick Blaise
  • Christophe Bergeron
  • Marcel Kool
  • Godelieve A M Tytgat
  • Marry M. Van Den Heuvel-Eibrink
  • Norbert Graf
  • Harm Van Tinteren
  • Aurore Coulomb
  • Manfred Gessler
  • Richard Dafydd Williams
  • Kathy Pritchard-Jones
Enheter & grupper
Externa organisationer
  • University College London
  • Hôpital Armand Trousseau
  • Julius Maximilian University of Würzburg
  • MRC-Holland
  • University Hospital of Wales
  • Cardiff University
  • Our Lady's Children's Hospital, Crumlin
  • Centre Léon Bérard
  • German Cancer Research Centre
  • Saarland University
  • Netherlands Cancer Institute
  • Paris-Sorbonne University
  • St. Anna Children's Hospital
  • Princess Maxima Center for Pediatric Oncology/Hematology
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
  • Pediatrik
Originalspråkengelska
Sidor (från-till)3195-3203
Antal sidor9
TidskriftJournal of Clinical Oncology
Volym34
Utgivningsnummer26
StatusPublished - 2016 sep 10
PublikationskategoriForskning
Peer review utfördJa