It’s All in the Genes: Pathogenic Variants in Hepatocellular Carcinoma

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Holly Magliochetti

Genetics Institute of America

Genetics Institute of America (GIA) is a national laboratory dedicated to heightening the awareness of early intervention and genetic screening to promote the longevity and quality of life outcomes.  


It’s All in the Genes: 

Pathogenic Germline Variants Identified for Hepatocellular Carcinoma

December 14, 2022

DELRAY BEACH, FL  – Hepatocellular carcinoma (HCC) has long been known to be caused by environmental and lifestyle factors, and, as a result, germline pathogenic and likely pathogenic (P/LP) variants have not been well-studied, despite evidence for potential familial inheritance. “As detection of inherited P/LP variants in cancer predisposition genes would have profound implications for surveillance and management of patients and their family members, it is important to know the yield of germline multigene panel testing in patients with HCC.”1

A recent study published in the American Society of Clinical Oncology’s Journal of Clinical Oncology by researchers from the University of Pennsylvania and Mayo Clinic aimed “to determine the rate of P/LP variants in patients with HCC, the possible associations with particular cancer predisposition genes, and the potential impact on clinical management, including surveillance and precision therapy.”1 Within the study’s cohorts, 11-14% of HCC patients had a P/LP variant, including variants in American College of Medical Genetics (ACMG) reportable genes (BRCA1, BRCA2, MSH2, TP53, and APC).1 Finding a P/LP variant changed the treatment plan for the patients in the cohort, opening opportunities for clinical trials, targeted therapeutics, and cascade testing.

Because HCC has been so closely associated with environmental factors, “this may help to explain the absence of established, clinical criteria-based recommendations for germline testing in patients with HCC.”1 “Universal testing [of HCC patients} should be considered” based on the study results, moving towards the universal germline testing of all cancer patients.1 The researchers hope that future studies will further investigate how these germline P/LP variants are affected by environmental factors, so that this information can be further applied into the clinical setting, increase survival rate and better treatment outcomes for HCC patients.

  1. Mezina A, Philips N, Bogus Z, et al. Multigene Panel Testing in Individuals With Hepatocellular Carcinoma Identifies Pathogenic Germline Variants. JCO Precis Oncol. 2021;5:PO.21.00079. Published 2021 Jun 10. doi:10.1200/PO.21.00079
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