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
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).
UR - http://www.scopus.com/inward/record.url?scp=85006269780&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006269780&partnerID=8YFLogxK
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 -