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

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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; Le Bouc, Yves; Ambros, Peter F.; Kager, Leo; O'Sullivan, Maureen J.; Blaise, Annick; Bergeron, Christophe; Mengelbier, Linda Holmquist; Gisselsson, David; Kool, Marcel; Tytgat, Godelieve A M; Van Den Heuvel-Eibrink, Marry M.; Graf, Norbert; Van Tinteren, Harm; Coulomb, Aurore; Gessler, Manfred; Williams, Richard Dafydd; Pritchard-Jones, Kathy.

In: Journal of Clinical Oncology, Vol. 34, No. 26, 10.09.2016, p. 3195-3203.

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Chagtai, T, Zill, C, Dainese, L, Wegert, J, Savola, S, Popov, S, Mifsud, W, Vujanić, G, Sebire, N, Le Bouc, Y, Ambros, PF, Kager, L, O'Sullivan, MJ, Blaise, A, Bergeron, C, Mengelbier, LH, Gisselsson, D, Kool, M, Tytgat, GAM, Van Den Heuvel-Eibrink, MM, Graf, N, Van Tinteren, H, Coulomb, A, Gessler, M, Williams, RD & Pritchard-Jones, K 2016, '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', Journal of Clinical Oncology, vol. 34, no. 26, pp. 3195-3203. https://doi.org/10.1200/JCO.2015.66.0001

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Chagtai T, Zill C, Dainese L, Wegert J, Savola S, Popov S, Mifsud W, Vujanić G, Sebire N, Le Bouc Y, Ambros PF, Kager L, O'Sullivan MJ, Blaise A, Bergeron C, Mengelbier LH, Gisselsson D, Kool M, Tytgat GAM, Van Den Heuvel-Eibrink MM, Graf N, Van Tinteren H, Coulomb A, Gessler M, Williams RD, Pritchard-Jones K. 2016. 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. Journal of Clinical Oncology. 34(26):3195-3203. https://doi.org/10.1200/JCO.2015.66.0001

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Chagtai, Tasnim ; Zill, Christina ; Dainese, Linda ; Wegert, Jenny ; Savola, Suvi ; Popov, Sergey ; Mifsud, William ; Vujanić, Gordan ; Sebire, Neil ; Le Bouc, Yves ; Ambros, Peter F. ; Kager, Leo ; O'Sullivan, Maureen J. ; Blaise, Annick ; Bergeron, Christophe ; Mengelbier, Linda Holmquist ; Gisselsson, David ; Kool, Marcel ; Tytgat, Godelieve A M ; Van Den Heuvel-Eibrink, Marry M. ; Graf, Norbert ; Van Tinteren, Harm ; Coulomb, Aurore ; Gessler, Manfred ; Williams, Richard Dafydd ; Pritchard-Jones, Kathy. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 26. pp. 3195-3203.

RIS

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 - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

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

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

VL - 34

SP - 3195

EP - 3203

JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

SN - 1527-7755

IS - 26

ER -