TY  - JOUR
A1  - Vujanić, Gordan M.
A1  - Gessler, Manfred
A1  - Ooms, Ariadne H. A. G.
A1  - Collini, Paola
A1  - Coulomb-l'Hermine, Aurore
A1  - D'Hooghe, Ellen
A1  - de Krijger, Ronald R.
A1  - Perotti, Daniela
A1  - Pritchard-Jones, Kathy
A1  - Vokuhl, Christian
A1  - van den Heuvel-Eibrink, Marry M.
A1  - Graf, Norbert
T1  - The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol
JF  - Nature Reviews Urology
N2  - On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel.
KW  - molecular biology
KW  - paediatric cancer
KW  - pathology
KW  - renal cancer
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233265
VL  - 15
ER  - 
TY  - JOUR
A1  - Chagtai, Tasnim
A1  - Zill, Christina
A1  - Dainese, Linda
A1  - Wegert, Jenny
A1  - Savola, Suvi
A1  - Popov, Sergey
A1  - Mifsud, William
A1  - Vujanic, Gordan
A1  - Sebire, Neil
A1  - Le Bouc, Yves
A1  - Ambros, Peter F.
A1  - Kager, Leo
A1  - O`Sullivan, Maureen J.
A1  - Blaise, Annick
A1  - Bergeron, Christophe
A1  - Holmquist Mengelbier, Linda
A1  - Gisselsson, David
A1  - Kool, Marcel
A1  - Tytgat, Godelieve A.M.
A1  - van den Heuvel-Eibrink, Marry M.
A1  - Graf, Norbert
A1  - van Tinteren, Harm
A1  - Coulomb, Aurore
A1  - Gessler, Manfred
A1  - Williams, Richard Dafydd
A1  - Pritchard-Jones, Kathy
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: a SIOP Renal Tumours Biology Consortium Study
JF  - Journal of Clinical Oncology
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.
KW  - Poor-prognosis
KW  - Mutations
KW  - Gene
KW  - Drosha
KW  - MYCN
KW  - Mechanisms
KW  - Reveals
KW  - Event
KW  - Relapse
KW  - Locus
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187478
VL  - 34
IS  - 26
ER  -