Dataset Information


MRNA profiles of 50 HB tumors

ABSTRACT: Hepatoblastoma (HB) is the most common liver cancer in children, but few pre-treatment tumors have been molecularly profiled. Consequently, there are no validated prognostic or therapeutic biomarkers for HB patients. We report on molecular analysis of 88 clinically-annotated HB tumors. This analysis pointed to three risk-stratifying molecular subtypes—low, intermediate and high risk—that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways. High-risk tumors are characterized by high NFE2L2 activity and LIN28B, HMGA2, SALL4 and AFP expression, low let-7 expression and HNF1A activity, and high coordinated expression of oncofetal proteins and stem cell markers. Tests on a 35 HB validation set supported these genes as prognostic biomarkers. 88 clinically-annotated frozen pre-clinical HB specimens with corresponding surgical pathology reports were included in the study (Table S1) following histological review. Specimens and clinical annotation were obtained from the COG Tumor Biospecimen Bank in Columbus, Ohio, the Pediatric Oncology Group Hepatoblastoma Biology Study P9346, and Texas-based institutions, under IRB-approved protocols. Whole exome sequencing (WES) was performed on 35 tumors for which matching normal DNA – either a blood sample or tumor-adjacent normal liver – was available (Table S2). Targeted sequencing of the CTNNB1 and NFE2L2 genes and the TERT promoter was completed on all 88 tumors. DNA from 47 HBs, including all 35 samples subjected to WES, was also analyzed by SNP array. RNA and miRNA expression profiling were performed on 50 and 57 tumors, respectively.

ORGANISM(S): Homo sapiens  

SUBMITTER: Dinesh Rakheja   Andras Heczey  Oliver A Hampton  Gail Tomlinson  Murali Chintagumpala  Kayuri Patel  Yidong Chen  Stephen F Sarabia  David A Wheeler  Lisa R Treviño  Pavel Sumazin  D W Parsons  Milton J Finegold  Patrick Thompson  Dolores López-Terrada  Sarah Comerford  Toni-Ann Mistretta  Rebecka Meyers  Barry Zorman 

PROVIDER: E-GEOD-75271 | ArrayExpress | 2015-11-28


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