TY - JOUR
T1 - 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
T2 - A SIOP renal tumours biology consortium study
AU - Chagtai, Tasnim
AU - Zill, Christina
AU - Dainese, Linda
AU - Wegert, Jenny
AU - Savola, Suvi
AU - Popov, Sergey
AU - Mifsud, William
AU - Vujanić, Gordan
AU - Sebire, Neil
AU - Le Bouc, Yves
AU - Ambros, Peter F.
AU - Kager, Leo
AU - O'Sullivan, Maureen J.
AU - Blaise, Annick
AU - Bergeron, Christophe
AU - Mengelbier, Linda Holmquist
AU - Gisselsson, David
AU - Kool, Marcel
AU - Tytgat, Godelieve A.M.
AU - Van Den Heuvel-Eibrink, Marry M.
AU - Graf, Norbert
AU - Van Tinteren, Harm
AU - Coulomb, Aurore
AU - Gessler, Manfred
AU - Williams, Richard Dafydd
AU - Pritchard-Jones, Kathy
N1 - Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2016/9/10
Y1 - 2016/9/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84989908986&partnerID=8YFLogxK
U2 - 10.1200/JCO.2015.66.0001
DO - 10.1200/JCO.2015.66.0001
M3 - Article
C2 - 27432915
AN - SCOPUS:84989908986
SN - 0732-183X
VL - 34
SP - 3195
EP - 3203
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 26
ER -