In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4724-4724
Kurzfassung:
Introduction Advances in chemotherapy and surgery have greatly improved overall survival rates of children with hepatoblastoma (HB). However, prognosis still remains quite poor for HB patients with high risk characteristics such as portal/hepatic venous macrovascular involvement, extrahepatic growth, high extent of the disease, and metastasis, as shown by studies of the International Childhood Liver Tumours Strategy Group (SIOPEL). The aim of our trinational study was to validate recently identified genetic and transcriptional characteristics of HB as prognostic biomarkers to aid development of a new risk stratification system based on clinical and biological factors. Experimental procedures Tumor tissue of a cohort of 171 hepatoblastoma patients from Germany, France and Spain was analyzed for mutations in CTNNB1, NFE2L2 and TERT (Eichenmüller et al., J Hepatol 2014; 61:1312-1320) by Sanger sequencing and the 16-gene signature (Cairo et al., Cancer Cell 2008; 14:471-84) by real-time PCR. Kaplan-Meier estimates of specific survival time in the various groups were compared using the log-rank Mantel-Cox test. Results Mutations of CTNNB1, NFE2L2, and TERT were found in 133 (78%), 10 (6%), and 10 (6%) patients, respectively. The adverse C2 subtype of the 16-gene signature was detected in 60 (35%) patients. Kaplan-Meier analyses depicted a significant association of the 16-gene signature (P & lt;0.0001) and NFE2L2 mutations (P & lt;0.0166) with poor outcome. Stratifying the patients of our cohort into a standard and high risk group based on the commonly used clinical SIOPEL criteria (Zsiros et al., J Clin Oncol 2010; 28:2584-2590) also revealed a strong association (P & lt;0.0001) of the high risk group with poor outcome. When added to the SIOPEL risk groups, presence of at least one biomarker could discriminate the SIOPEL high risk patients into an intermediate and a very high risk group (P & lt;0.0001), whereas biomarker positive and negative standard risk patients showed no difference in outcome. Conclusions We have validated the 16-gene signature and NFE2L2 mutations as highly prognostic biomarkers in HB and propose a new stratification system that is based on the combination of clinical and biological factors, which might facilitate more tailored and risk-adapted therapies and thus better outcome of high risk patients in the future. Citation Format: Stefano Cairo, Carolina Armengol, Beate Häberle, Marina Simon-Coma, Catherine Guettier, Ivo Leuschner, Marie-Annick Buendia, Dietrich von Schweinitz, Roland Kappler. Combined clinical and biological risk stratification in pediatric hepatoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4724. doi:10.1158/1538-7445.AM2017-4724
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-4724
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2017
ZDB Id:
2036785-5
ZDB Id:
1432-1
