Reconciling the Biological and Transcriptional Variability of Hepatoblastoma with Its Mutational Uniformity.
Simple Summary: Hepatoblastoma (HB), the most common form of childhood liver cancer, is associated with dual mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways in ~50% of cases. However, this mutational simplicity cannot explain HB's biological and histologic diversity. This discu...
| Publicado en: | Cancers Vol. 13; no. 9; pp. 1996 - 1997 |
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| Autores principales: | , |
| Formato: | pictorial review tables/charts Journal Article |
| Publicado: |
MDPI
May2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=150367760&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 150367760 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: May2021 vid: 13 iid: 9 pid: 97109 pub: MDPI artinfo: ui: 150367760 150367760 150367760 10.3390/cancers13091996 150367760 ppf: 1996 ppct: 1 formats: tig: atl: Reconciling the Biological and Transcriptional Variability of Hepatoblastoma with Its Mutational Uniformity. aug: au: Prochownik, Edward V. Kappler, Roland affil: Division of Hematology/Oncology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA sug: subj: Liver Neoplasms Physiopathology Mutation Neoplasms by Histologic Type Cytoskeletal Proteins Metabolism Signal Transduction Transcription Factors Metabolism Gene Expression Disease Progression ab: Simple Summary: Hepatoblastoma (HB), the most common form of childhood liver cancer, is associated with dual mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways in ~50% of cases. However, this mutational simplicity cannot explain HB's biological and histologic diversity. This discussion focuses upon recent work showing that specific β-catenin mutants are key determinants of this HB variability as well as their metabolic and transcriptional signatures. Dysregulation of the anti-oxidant NFE2L2 pathway also contributes to tumorigenesis by being directly transforming in association with either of the other two factors. The transcriptional overlap of tumors generated by pairs of factors identifies crucial targets that likely mediate HB tumorigenesis, behavior and appearance. Hepatoblastoma (HB), the most common childhood liver cancer, is associated with seven distinct histologic subtypes and variable degrees of clinical aggressiveness and presentation. Yet it is among the least genomically altered tumors known, with about half of HBs showing mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways. This raises the question of how this mutational simplicity can generate such biological and histologic complexity. Recent work shows that the identity of the underlying β-catenin mutation is a major contributor. Mutation or over-expression of the NFE2L2/NRF2 transcription factor, previously thought only to promote anti-oxidant responses, has also recently been shown to accelerate the growth of HBs generated by mutations in the Wnt/β-catenin and Hippo pathways while imparting novel features such as the tumor-associated cysts and necrosis. Moreover, patient-associated NFE2L2 mutations are overtly transforming when co-expressed with either mutant β-catenin or a Hippo pathway effector. The finding that tumorigenesis can be driven by any two arms of the β-catenin/Hippo/NFE2L2 axis has permitted the identification of a small subset of coordinately regulated tumor-specific transcripts, some of whose levels correlate with inferior long-term outcomes in HB and other cancers. Collectively, these findings begin to provide for more refined and molecularly based classification, survival algorithms and design of chemotherapeutic regimens. pubtype: Academic Journal doctype: pictorial review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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