title: Liver cancer with concomitant TP53 and CTNNB1 mutations: a case report.
abstract: BACKGROUND
  In the spectrum of molecular alterations found in hepatocellular carcinoma (HCC), somatic mutations in the WNT/β-catenin pathway and the p53/cell cycle control pathway are among the most frequent ones. It has been suggested that both mutations occur in a mutually exclusive manner and they are used as molecular classifiers in HCC classification proposals.
  
  
  METHODS
  Here, we report the case of a treatment-naïve mixed hepatocellular/cholangiocellular carcinoma (HCC/CCC) with morphological and genetic intratumor heterogeneity. Within the predominant part of the tumor with hepatocellular differentiation, a p.D32V mutation in exon 3 of the CTNNB1 gene occurred concomitantly with a TP53 intron 7/exon 8 splice site mutation.
  
  
  CONCLUSIONS
  Intratumor heterogeneity challenges the concept of CTNNB1 and TP53 gene mutations being mutually exclusive molecular classifiers in HCC, which has implications for HCC classification approaches.
authors.affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland ; Leibniz Institute for Prevention Research and Epidemiology (BIPS), Bremen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Friemel
authors.affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rechsteiner
authors.affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Marion
authors.initials: M
authors.lastname: Bawohl
authors.affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland ; Swiss Hepato-Pancreato-Biliary Center, Department of Digestive and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Frick
authors.affiliation: Clinics of Hepatology and Gastroenterology, University and University Hospital Zurich, Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Swiss Hepato-Pancreato-Biliary Center, Department of Digestive and Transplant Surgery, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Lesurtel
authors.affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
keywords: CTNNB1; Hepatocellular carcinoma (HCC); Intratumor heterogeneity; Next generation sequencing; TP53