Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups

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

doi:10.1002/hep.28888

Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

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. 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).

Original language	English (US)
Pages (from-to)	104-121
Number of pages	18
Journal	Hepatology
Volume	65
Issue number	1
DOIs	https://doi.org/10.1002/hep.28888
State	Published - Jan 1 2017

ASJC Scopus subject areas

Hepatology

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10.1002/hep.28888

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Sumazin, P., Chen, Y., Treviño, L. R., Sarabia, S. F., Hampton, O. A., Patel, K., Mistretta, T. A., Zorman, B., Thompson, P., Heczey, A., Comerford, S., Wheeler, D. A., Chintagumpala, M., Meyers, R., Rakheja, D., Finegold, M. J., Tomlinson, G., Parsons, D. W., & López-Terrada, D. (2017). Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups. Hepatology, 65(1), 104-121. https://doi.org/10.1002/hep.28888

Sumazin, P, Chen, Y, Treviño, LR, Sarabia, SF, Hampton, OA, Patel, K, Mistretta, TA, Zorman, B, Thompson, P, Heczey, A, Comerford, S, Wheeler, DA, Chintagumpala, M, Meyers, R, Rakheja, D, Finegold, MJ, Tomlinson, G, Parsons, DW & López-Terrada, D 2017, 'Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups', Hepatology, vol. 65, no. 1, pp. 104-121. https://doi.org/10.1002/hep.28888

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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. 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).",

author = "Pavel Sumazin and Yidong Chen and Trevi{\~n}o, {Lisa R.} and Sarabia, {Stephen F.} and Hampton, {Oliver A.} and Kayuri Patel and Mistretta, {Toni Ann} and Barry Zorman and Patrick Thompson and Andras Heczey and Sarah Comerford and Wheeler, {David A.} and Murali Chintagumpala and Rebecka Meyers and Dinesh Rakheja and Finegold, {Milton J.} and Gail Tomlinson and Parsons, {D. Williams} and Dolores L{\'o}pez-Terrada",

note = "Publisher Copyright: {\textcopyright} 2016 by the American Association for the Study of Liver Diseases.",

year = "2017",

month = jan,

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doi = "10.1002/hep.28888",

language = "English (US)",

volume = "65",

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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).

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Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups

Abstract

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