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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; Vujanić, Gordan; Sebire, Neil and Le Bouc, Yves, et al. (2016) In Journal of Clinical Oncology 34(26). p.3195-3203
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... (More)

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.

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Journal of Clinical Oncology
volume
34
issue
26
pages
9 pages
publisher
American Society of Clinical Oncology
external identifiers
  • scopus:84989908986
  • wos:000382473000013
ISSN
0732-183X
DOI
10.1200/JCO.2015.66.0001
language
English
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yes
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0437140a-1589-498b-ac0f-9e4fd7e569e6
date added to LUP
2016-12-01 10:09:52
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2017-10-22 05:22:48
@article{0437140a-1589-498b-ac0f-9e4fd7e569e6,
  abstract     = {<p>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 &lt; .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.</p>},
  author       = {Chagtai, Tasnim and Zill, Christina and Dainese, Linda and Wegert, Jenny and Savola, Suvi and Popov, Sergey and Mifsud, William and Vujanić, Gordan and Sebire, Neil and Le Bouc, Yves and Ambros, Peter F. and Kager, Leo and O'Sullivan, Maureen J. and Blaise, Annick and Bergeron, Christophe and Mengelbier, Linda Holmquist and Gisselsson, David and Kool, Marcel and Tytgat, Godelieve A M and Van Den Heuvel-Eibrink, Marry M. and Graf, Norbert and Van Tinteren, Harm and Coulomb, Aurore and Gessler, Manfred and Williams, Richard Dafydd and Pritchard-Jones, Kathy},
  issn         = {0732-183X},
  language     = {eng},
  month        = {09},
  number       = {26},
  pages        = {3195--3203},
  publisher    = {American Society of Clinical Oncology},
  series       = {Journal of Clinical Oncology},
  title        = {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},
  url          = {http://dx.doi.org/10.1200/JCO.2015.66.0001},
  volume       = {34},
  year         = {2016},
}