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Hepatology (Baltimore, Md.) · 2016

Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Sumazin Pavel, Chen Yidong, Treviño Lisa R, Sarabia Stephen F, Hampton Oliver A, Patel Kayuri, Mistretta Toni-Ann, Zorman Barry, Thompson Patrick, Heczey Andras, Comerford Sarah, Wheeler David A, Chintagumpala Murali, Meyers Rebecka, Rakheja Dinesh, Finegold Milton J, Tomlinson Gail, Parsons D Williams, López-Terrada Dolores

Аннотация

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).

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