title: Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.
abstract: Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity.
  
  
  
  Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121).
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
authors: Pavel
authors: P
authors: Sumazin
authors: Departments of Epidemiology and Biostatistics, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors: Yidong
authors: Y
authors: Chen
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.
authors: Lisa R
authors: LR
authors: Treviño
authors: Pathology & Immunology, Baylor College of Medicine, Houston, TX.
authors: Stephen F
authors: SF
authors: Sarabia
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.
authors: Oliver A
authors: OA
authors: Hampton
authors: Pathology & Immunology, Baylor College of Medicine, Houston, TX.
authors: Kayuri
authors: K
authors: Patel
authors: Pathology & Immunology, Baylor College of Medicine, Houston, TX.
authors: Toni-Ann
authors: TA
authors: Mistretta
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors: Barry
authors: B
authors: Zorman
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors: Patrick
authors: P
authors: Thompson
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
authors: Andras
authors: A
authors: Heczey
authors: Departments of Molecular Genetics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Sarah
authors: S
authors: Comerford
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.
authors: David A
authors: DA
authors: Wheeler
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
authors: Murali
authors: M
authors: Chintagumpala
authors: Department of Pediatric Surgery, University of Utah, Salt Lake City, UT.
authors: Rebecka
authors: R
authors: Meyers
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Dinesh
authors: D
authors: Rakheja
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.|Pathology & Immunology, Baylor College of Medicine, Houston, TX.
authors: Milton J
authors: MJ
authors: Finegold
authors: Departments of Pediatric Hematology and Oncology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors: Gail
authors: G
authors: Tomlinson
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.
authors: D Williams
authors: DW
authors: Parsons
authors: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.|Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.|Pathology & Immunology, Baylor College of Medicine, Houston, TX.
authors: Dolores
authors: D
authors: López-Terrada
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D018197:Hepatoblastoma / Q000145:classification / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000145:classification / Q000235:genetics*; D011379:Prognosis