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Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids

Hanbing Song, Simon Bucher, Katherine Rosenberg, Margaret Tsui, Deviana Burhan, Daniel Hoffman, Soo-Jin Cho, Arun Rangaswami, Marcus Breese, Stanley Leung, María V. Pons Ventura, E. Alejandro Sweet-Cordero, Franklin W. Huang (), Amar Nijagal () and Bruce Wang ()
Additional contact information
Hanbing Song: University of California, San Francisco
Simon Bucher: University of California, San Francisco
Katherine Rosenberg: University of California, San Francisco
Margaret Tsui: University of California, San Francisco
Deviana Burhan: University of California, San Francisco
Daniel Hoffman: University of California, San Francisco
Soo-Jin Cho: University of California, San Francisco
Arun Rangaswami: The Pediatric Liver Center at UCSF Benioff Childrens’ Hospitals
Marcus Breese: University of California, San Francisco
Stanley Leung: University of California, San Francisco
María V. Pons Ventura: University of California, San Francisco
E. Alejandro Sweet-Cordero: The Pediatric Liver Center at UCSF Benioff Childrens’ Hospitals
Franklin W. Huang: University of California, San Francisco
Amar Nijagal: University of California, San Francisco
Bruce Wang: University of California, San Francisco

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Pediatric hepatoblastoma is the most common primary liver cancer in infants and children. Studies of hepatoblastoma that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, hepatoblastoma tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we use single-cell transcriptomic techniques to analyze resected human pediatric hepatoblastoma specimens, and identify five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease. Notably, patient-derived hepatoblastoma spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. In this work, we define hepatoblastoma tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32473-z

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DOI: 10.1038/s41467-022-32473-z

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