Molecular profiling identifies new high-risk subtype of pediatric liver cancer

Until recently, almost all pediatric liver cancers were classified as hepatoblastoma or hepatocellular carcinoma. However, pediatric pathologists have observed that some liver tumors have histological features that do not readily match either of these two models of carcinoma. These cancers are less likely to respond to chemotherapy and patient outcomes are poor.

First author Dr. Pavel Sumazin, associate professor of pediatrics at Baylor College of Medicine and Texas Children’s Cancer and Hematology Center, and his colleagues sought to better characterize this high-risk cancer.

The researchers examined the molecular profiles of the tumors, including genetic alterations and gene expression profiles. They found that these profiles do not fit into the molecular categories of hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Instead, these tumors exhibited recurrent molecular features that have been observed in both HB and HCC. They designated these tumors as hepatoblastomas with features of hepatocellular carcinoma (HBC).

The team also looked at HBC treatments and outcomes and found that they tended to be more resistant to standard chemotherapy and to have poor outcomes when left untreated with more aggressive surgical approaches, including the transplant. Based on their findings, the team proposed a diagnostic algorithm to stratify HBCs and guide specialized treatment.

“Our results highlight the importance of molecular testing to accurately classify these tumors to optimize treatment recommendations at the time of initial diagnosis,” said Dr. Dolores López-Terrada, corresponding author of the paper, professor of pathology , Immunology and Pediatrics at Baylor and Chief of the Division of Genomic Medicine at Texas Children’s. “Our analysis suggested that children with CHB may benefit from treatment strategies that differ from guidelines for patients with hepatoblastoma and hepatocellular carcinoma.”

Find all the details of this study in the Journal of Hepatology.

Sumazin and López-Terrada are both members of the Dan L Duncan Comprehensive Cancer Center at Baylor. Other Baylor and Texas Children’s authors include Tricia L. Peters, Stephen F. Sarabia, Hyunjae R. Kim, Martin Urbicain, Emporia Faith Hollingsworth, Karla R. Alvarez, Cintia R. Perez, Mohammad Javad Najaf Panah, Jessica L. Epps, Kathy Scorsone, Barry Zorman, Sarah E. Woodfield, John A. Goss, Sanjeev A. Vasudevan, Andras Heczey, Angshumoy Roy, Kevin E. Fisher, Kalyani R. Patel, and Milton J. Finegold. Howard Katzenstein, Allison F. O’Neill, Rebecka Meyers, Greg Tiao, Jim Geller, Sarangarajan Ranganathan, Arun A. Rangaswami, all members of the Children’s Oncology Group Liver Tumor Committee, and Rita Alaggio and Alice Pozza also contributed. They come from the following institutions: Wolfson Children’s Hospital, Dana-Farber Cancer Institute, Boston Children’s Hospital, Harvard Medical School, Primary Children’s Hospital, Cincinnati Children’s Hospital Medical Center, University of California San Francisco and Bambino Gesù Children’s Hospital.

This work was funded by the Cancer Prevention and Research Institute of Texas (RP180674), European Union Horizon 2020 (826121), Schindler Foundation, and National Cancer Institute (R21CA223140).

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Materials provided by Baylor College of Medicine. Original written by Molly Chiu. Note: Content may be edited for style and length.

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