Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification.

Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification. Research Abstract Details 

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Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification. Abstract Text:

X Liu,P Mazanek,V Dam,Q Wang,H Zhao,R Guo,J Jagannathan,A Cnaan,J M Maris,M D Hogarty,

Neuroblastoma (NB) is a frequently lethal tumor of childhood. MYCN amplification accounts for the aggressive phenotype in a subset while the majority have no consistently identified molecular aberration but frequently express MYC at high levels. We hypothesized that activated Wnt/beta-catenin (CTNNB1) signaling might account for this as MYC is a beta-catenin transcriptional target and multiple embryonal and neural crest malignancies have oncogenic alterations in this pathway. NB cell lines without MYCN amplification express higher levels of MYC and beta-catenin (with aberrant nuclear localization) than MYCN-amplified cell lines. Evidence for aberrant beta-catenin-TCF transcriptional activity was demonstrated using expression profiles from 73 primary NBs. Findings included increased WNT ligands (WNT1, WNT6, WNT7A, WNT10B), DVL1 and TCF7 expression in high-risk NBs without MYCN amplification, consistent with canonical beta-catenin signaling. More directly, Patterns of Gene Expression and Gene Set Enrichment Analyses demonstrated beta-catenin target genes (for example, MYC, PPARD, NRCAM, CD44, TCF7) as coordinately upregulated in high-risk NBs without MYCN amplification in comparison to high-risk MYCN-amplified or intermediate-risk NBs, supporting pathway activation in this subset. Thus, high-risk NBs without MYCN amplification may deregulate MYC and other oncogenic genes via altered beta-catenin signaling providing a potential candidate pathway for therapeutic inhibition.Oncogene (2008) 27, 1478-1488; doi:10.1038/sj.onc.1210769; published online 27 August 2007.

Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification. Publishing Authors By Initials

X Liu,P Mazanek,V Dam,Q Wang,H Zhao,R Guo,J Jagannathan,A Cnaan,JM Maris,MD Hogarty,

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Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Oncogene

VOLUME: 27

Page Numbers: 1478-88

Journal Abbreviation: Oncogene

ISSN: 1476-5594

DAY: 27

MONTH: 08

YEAR: 2007

Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

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AFFILIATION: 1Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Country: England

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MEDLINETA: Oncogene

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