Cancer predisposition signaling in Beckwith-Wiedemann Syndrome drives Wilms tumor development.
Br J Cancer
; 130(4): 638-650, 2024 03.
Article
en En
| MEDLINE
| ID: mdl-38142265
ABSTRACT
BACKGROUND:
Wilms tumor (WT) exhibits structural and epigenetic changes at chromosome 11p15, which also cause Beckwith-Wiedemann Syndrome (BWS). Children diagnosed with BWS have increased risk for WT. The aim of this study is to identify the molecular signaling signatures in BWS driving these tumors.METHODS:
We performed whole exome sequencing, methylation array analysis, and gene expression analysis on BWS-WT samples. Our data were compared to publicly available nonBWS data. We categorized WT from BWS and nonBWS patients by assessment of 11p15 methylation status and defined 5 groups- control kidney, BWS-nontumor kidney, BWS-WT, normal-11p15 nonBWS-WT, altered-11p15 nonBWS-WT.RESULTS:
BWS-WT samples showed single nucleotide variants in BCORL1, ASXL1, ATM and AXL but absence of recurrent gene mutations associated with sporadic WT. We defined a narrow methylation range stratifying nonBWS-WT samples. BWS-WT and altered-11p15 nonBWS-WT showed enrichment of common and unique molecular signatures based on global differential methylation and gene expression analysis. CTNNB1 overexpression and broad range of interactions were seen in the BWS-WT interactome study.CONCLUSION:
While WT predisposition in BWS is well-established, as are 11p15 alterations in nonBWS-WT, this study focused on stratifying tumor genomics by 11p15 status. Further investigation of our findings may identify novel therapeutic targets in WT oncogenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Beckwith-Wiedemann
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Tumor de Wilms
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Neoplasias Renales
Límite:
Child
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article