Cancers (Dec 2022)
Low Frequency of Cancer-Predisposition Gene Mutations in Liver Transplant Candidates with Hepatocellular Carcinoma
- Klara Horackova,
- Sona Frankova,
- Petra Zemankova,
- Petr Nehasil,
- Marta Cerna,
- Magdalena Neroldova,
- Barbora Otahalova,
- Jan Kral,
- Milena Hovhannisyan,
- Viktor Stranecky,
- Tomas Zima,
- Marketa Safarikova,
- Marta Kalousova,
- CZECANCA Consortium,
- Jan Novotny,
- Jan Sperl,
- Marianna Borecka,
- Sandra Jelinkova,
- Michal Vocka,
- Marketa Janatova,
- Petra Kleiblova,
- Zdenek Kleibl,
- Milan Jirsa,
- Jana Soukupova
Affiliations
- Klara Horackova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Sona Frankova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic
- Petra Zemankova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Petr Nehasil
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Marta Cerna
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Magdalena Neroldova
- Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic
- Barbora Otahalova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Jan Kral
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Milena Hovhannisyan
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Viktor Stranecky
- Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Tomas Zima
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Marketa Safarikova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Marta Kalousova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- CZECANCA Consortium
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Jan Novotny
- Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic
- Jan Sperl
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic
- Marianna Borecka
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Sandra Jelinkova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Michal Vocka
- Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Marketa Janatova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Petra Kleiblova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Zdenek Kleibl
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Milan Jirsa
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Jana Soukupova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- DOI
- https://doi.org/10.3390/cancers15010201
- Journal volume & issue
-
Vol. 15,
no. 1
p. 201
Abstract
Hepatocellular carcinoma (HCC) mainly stems from liver cirrhosis and its genetic predisposition is believed to be rare. However, two recent studies describe pathogenic/likely pathogenic germline variants (PV) in cancer-predisposition genes (CPG). As the risk of de novo tumors might be increased in PV carriers, especially in immunosuppressed patients after a liver transplantation, we analyzed the prevalence of germline CPG variants in HCC patients considered for liver transplantation. Using the panel NGS targeting 226 CPGs, we analyzed germline DNA from 334 Czech HCC patients and 1662 population-matched controls. We identified 48 PVs in 35 genes in 47/334 patients (14.1%). However, only 7/334 (2.1%) patients carried a PV in an established CPG (PMS2, 4×NBN, FH or RET). Only the PV carriers in two MRN complex genes (NBN and RAD50) were significantly more frequent among patients over controls. We found no differences in clinicopathological characteristics between carriers and non-carriers. Our study indicated that the genetic component of HCC is rare. The HCC diagnosis itself does not meet criteria for routine germline CPG genetic testing. However, a low proportion of PV carriers may benefit from a tailored follow-up or targeted therapy and germline testing could be considered in liver transplant recipients.
Keywords
- hepatocellular carcinoma
- liver cirrhosis
- liver transplantation
- genetic predisposition
- panel sequencing
- MRN complex