Title | Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Sumazin, P, Chen, Y, Treviño, LR, Sarabia, SF, Hampton, OA, Patel, K, Mistretta, T-A, Zorman, B, Thompson, P, Heczey, A, Comerford, S, Wheeler, DA, Chintagumpala, M, Meyers, R, Rakheja, D, Finegold, MJ, Tomlinson, G, D Parsons, W, López-Terrada, D |
Journal | Hepatology |
Volume | 65 |
Issue | 1 |
Pagination | 104-121 |
Date Published | 2017 Jan |
ISSN | 1527-3350 |
Keywords | Gene Expression Regulation, Neoplastic, Genomics, Hepatoblastoma, Humans, Liver Neoplasms, Prognosis |
Abstract | UNLABELLED: 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). |
DOI | 10.1002/hep.28888 |
Alternate Journal | Hepatology |
PubMed ID | 27775819 |
Grant List | K12 CA090433 / CA / NCI NIH HHS / United States U10 CA098543 / CA / NCI NIH HHS / United States P30 DK056338 / DK / NIDDK NIH HHS / United States |
Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.
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