TY - JOUR
T1 - Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups
AU - Sumazin, Pavel
AU - Chen, Yidong
AU - Treviño, Lisa R.
AU - Sarabia, Stephen F.
AU - Hampton, Oliver A.
AU - Patel, Kayuri
AU - Mistretta, Toni Ann
AU - Zorman, Barry
AU - Thompson, Patrick
AU - Heczey, Andras
AU - Comerford, Sarah
AU - Wheeler, David A.
AU - Chintagumpala, Murali
AU - Meyers, Rebecka
AU - Rakheja, Dinesh
AU - Finegold, Milton J.
AU - Tomlinson, Gail
AU - Parsons, D. Williams
AU - López-Terrada, Dolores
N1 - Funding Information:
We are grateful to the Children's Oncology Group Rare Tumor Committee and Liver Tumor Subcommittee for their support, Angela Major and Pamela Parsons who performed the immunohistochemical studies, and Karen Prince and Faith Hollingsworth for their valuable help with the preparation of the manuscript.
Publisher Copyright:
© 2016 by the American Association for the Study of Liver Diseases.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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. Conclusion: 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).
AB - 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. Conclusion: 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).
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U2 - 10.1002/hep.28888
DO - 10.1002/hep.28888
M3 - Article
C2 - 27775819
AN - SCOPUS:85006269780
VL - 65
SP - 104
EP - 121
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 1
ER -