title: Multiple β-catenin mutations in hepatocellular lesions arising in Abernethy malformation.
abstract: An 18-year-old man underwent liver transplantation due to an Abernethy malformation associated with multiple hepatocellular nodules including one which was rapidly enlarging and was suspicious for malignant transformation. Analysis of the explanted liver showed a spectrum of multiple hepatocellular nodules ranging in appearance from focal nodular hyperplasia, hepatocellular adenoma and to a well-differentiated hepatocellular neoplasm borderline for hepatocellular carcinoma. Mutational analysis revealed wild-type β-catenin expression in the background liver and some nodules, whilst different variants were present in other lesions irrespective of their morphological appearance. No telomerase reverse transcriptase (TERT) promoter mutation was identified. Abernethy malformations can lead to independent genetic events which can result in β-catenin mutations associated with malignant transformation of hepatocellular nodules. When following up such patients, one must therefore have a high index of suspicion, particularly if radiological surveillance reveals a change in the nature of hepatic lesions.
authors.affiliation: Histopathology Department, King's College Hospital, London, UK SE5 9RS.
authors.forename: Tracy
authors.initials: T
authors.lastname: Sorkin
authors.affiliation: Liver Molecular Genetics, King's College Hospital, London, UK SE5 9RS.
authors.forename: Sandra
authors.initials: S
authors.lastname: Strautnieks
authors.affiliation: Liver Molecular Genetics, King's College Hospital, London, UK SE5 9RS.
authors.forename: Pierre
authors.initials: P
authors.lastname: Foskett
authors.affiliation: Radiology Department, King's College Hospital, London, UK SE5 9RS.
authors.forename: Praveen
authors.initials: P
authors.lastname: Peddu
authors.affiliation: Liver Molecular Genetics, King's College Hospital, London, UK SE5 9RS; Institute of Liver Studies, King's College London, London, UK SE5 9RS.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thompson
authors.affiliation: Institute of Liver Studies, King's College London, London, UK SE5 9RS.
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
authors.affiliation: Institute of Liver Studies, King's College London, London, UK SE5 9RS. Electronic address: alberto.quaglia@nhs.net.
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
mesh_terms: D018248:Adenoma, Liver Cell / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D020518:Focal Nodular Hyperplasia / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D020022:Genetic Predisposition to Disease; D005974:Glutamate-Ammonia Ligase / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D016031:Liver Transplantation; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D010641:Phenotype; D054079:Vascular Malformations / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D051176:beta Catenin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin; D005974:Glutamate-Ammonia Ligase
keywords: Abernethy malformation; Focal nodular hyperplasia; Glutamine synthetase; Hepatocellular adenoma; Hepatocellular carcinoma; Porto-systemic shunt; β-catenin