Volume 62, Issue 3, Pages 734-738 (March 2015) Biallelic inactivation of protoporphyrinogen oxidase and hydroxymethylbilane synthase is associated with liver cancer in acute porphyrias  Xiaoye Schneider-Yin, Anne-Moon van Tuyll van Serooskerken, Marko Siegesmund, Philip Went, Jasmin Barman-Aksözen, Reno S. Bladergroen, Paul Komminoth, Roy H.E. Cloots, Véronique J. Winnepenninckx, Axel zur Hausen, Markus Weber, Ann Driessen, Pamela Poblete-Gutiérrez, Peter Bauer, Christopher Schroeder, Michel van Geel, Elisabeth I. Minder, Jorge Frank  Journal of Hepatology  Volume 62, Issue 3, Pages 734-738 (March 2015) DOI: 10.1016/j.jhep.2014.11.029 Copyright © 2014 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Sequence analyses of the PPOX and HMBS genes in patients with acute porphyria and hepatocellular carcinoma. Partial sequences of the PPOX gene, obtained by analyzing the liver cancer tissue from a VP patient, show (A) an insertion of nucleotide C at position 1080 (c.1082dupC) in exon 10 and (B) a nonsense mutation p.Lys416stop (AAG→TAG) in exon 11. Partial sequence of the HMBS gene, obtained by analyzing the liver cancer tissue from an AIP patient, show (C) a missense mutation p.Gly111Arg (GGA→AGA) in exon 7 and (D) a nonsense mutation p.Leu220stop (TTG→TAG) in exon 12. (This figure appears in color on the web.) Journal of Hepatology 2015 62, 734-738DOI: (10.1016/j.jhep.2014.11.029) Copyright © 2014 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Microscopic examination of hepatic tumor tissues. (A) HePar-1 and (B) glypican-3 immunostaining of the hepatic tumor tissue from a VP patient (20×). (C) Immunohistochemical assessment of PPOX in the VP patient. Note the almost complete absence of PPOX expression in the cancerous liver tissue as compared to the non-cancerous liver section. (D) Immunohistochemical assessment of PPOX in a non-porphyric control individual with HCC. No differences in PPOX expression are detectable comparing the cancerous and non-cancerous liver sections. (C and D: 10×). (This figure appears in color on the web.) Journal of Hepatology 2015 62, 734-738DOI: (10.1016/j.jhep.2014.11.029) Copyright © 2014 European Association for the Study of the Liver Terms and Conditions