Hepatoblastoma is the most common form of liver cancer in children. It is diagnosed during the first three years of life. Now, a new University of California, San Francisco (UCSF) study gives hope to working toward more precise chemotherapy treatment for hepatoblastoma. The study exposes the diversity within the most common type of pediatric liver tumor.

The findings are published in Nature Communications in a paper titled, “Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids.”

“Pediatric hepatoblastoma is the most common primary liver cancer in infants and children,” wrote the researchers. “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.”

A team of researchers from three different UCSF labs used single-cell transcriptomic techniques to analyze resected human pediatric hepatoblastoma specimens. The researchers identified five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease.

“Many pediatric tumors originate from an embryonic cell and some are bland in terms of their mutational burden,” said study co-author Amar Nijagal, assistant professor in the division of pediatric surgery at UCSF Benioff Children’s Hospital, San Francisco. “The fact that this tumor has significant heterogeneity made us question what was driving this heterogeneity, and we wanted to learn more.”

Aside from offering hope for better treatment, studying hepatoblastoma provides a window into how tissues develop normally, Nijagal said.

“Normal development and cancer are two sides of the same coin,” Nijagal said. “Here you have a tumor that is not acquired, as many adult tumors are from something like smoking or excess UV exposure. Instead, something goes wrong during development to set off these hepatoblasts towards developing into a malignancy. So we are interested in learning what are the signals—such as those from immune cells—that maintain normal development.”

The study results help illuminate the foundation of HB tumor heterogeneity and demonstrate that patient-specific spheroids can be used to predict treatment response and identify therapeutic targets.

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