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Background <p>Beckwith-Wiedemann syndrome (BWS) is an overgrowth and cancer predisposition syndrome caused by epigenetic alterations on chromosome 11p15 that predisposes children to multiple cancer types, including hepatoblastoma. Hepatoblastoma is heterogenous in nature, and the 11p15 changes that cause BWS can also be found as a somatic alteration in nonBWS hepatoblastomas, further adding complexity to this disease.</p> Methods <p>To understand the impact of the predisposition molecular cues in BWS hepatoblastoma, we interrogated BWS and nonBWS hepatoblastomas, as well as adjacent normal liver, using a multiomic approach [single nuclei RNA-sequencing (snRNA-seq) + single nuclei assay for transposable-accessible chromatin sequencing (snATAC-seq)].</p> Results <p>Our approach identified an enrichment of the WNT signaling pathway in BWS hepatoblastoma. Despite similar histology, we found greater tumour heterogeneity and embryonic transcriptional signatures in BWS hepatoblastoma. Furthermore, using pseudotime analysis, we identified a population of transition cells in BWS, with unique molecular profiles, which likely promote the precancer to cancer neoplastic transition in BWS.</p> Conclusions <p>This study highlights key signaling pathways, particularly WNT, and identifies a unique population of intermediate/transition cells that may drive neoplastic transformation in BWS hepatoblastoma. These findings provide new insights into the molecular events leading to cancer in BWS and suggest potential targets for early intervention and prevention strategies.</p> <p></p>

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Beckwith-Wiedemann syndrome multiomic analysis of hepatoblastoma uncovers unique tumour heterogeneity and cellular landscapes, including transition cells leading to tumour formation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Snehal Nirgude,
  • Elisia D. Tichy,
  • Yuanchao Zhang,
  • Khanh B. Trang,
  • Rose D. Pradieu,
  • Michael Xie,
  • Kathrin M. Bernt,
  • Suzanne P. MacFarland,
  • Jennifer M. Kalish

摘要

Background

Beckwith-Wiedemann syndrome (BWS) is an overgrowth and cancer predisposition syndrome caused by epigenetic alterations on chromosome 11p15 that predisposes children to multiple cancer types, including hepatoblastoma. Hepatoblastoma is heterogenous in nature, and the 11p15 changes that cause BWS can also be found as a somatic alteration in nonBWS hepatoblastomas, further adding complexity to this disease.

Methods

To understand the impact of the predisposition molecular cues in BWS hepatoblastoma, we interrogated BWS and nonBWS hepatoblastomas, as well as adjacent normal liver, using a multiomic approach [single nuclei RNA-sequencing (snRNA-seq) + single nuclei assay for transposable-accessible chromatin sequencing (snATAC-seq)].

Results

Our approach identified an enrichment of the WNT signaling pathway in BWS hepatoblastoma. Despite similar histology, we found greater tumour heterogeneity and embryonic transcriptional signatures in BWS hepatoblastoma. Furthermore, using pseudotime analysis, we identified a population of transition cells in BWS, with unique molecular profiles, which likely promote the precancer to cancer neoplastic transition in BWS.

Conclusions

This study highlights key signaling pathways, particularly WNT, and identifies a unique population of intermediate/transition cells that may drive neoplastic transformation in BWS hepatoblastoma. These findings provide new insights into the molecular events leading to cancer in BWS and suggest potential targets for early intervention and prevention strategies.