Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I

被引：114

作者：

Calderaro, Julien ^{[1
,2
,3
,4
]}

Labrune, Philippe ^{[5
,6
]}

Morcrette, Guillaume ^{[1
,2
]}

Rebouissou, Sandra ^{[1
,2
]}

Franco, Dominique ^{[7
]}

Prevot, Sophie ^{[8
]}

Quaglia, Alberto ^{[9
]}

Bedossa, Pierre ^{[10
]}

Libbrecht, Louis ^{[11
]}

Terracciano, Luigi ^{[12
]}

Smit, G. Peter A. ^{[13
]}

Bioulac-Sage, Paulette ^{[14
,15
]}

Zucman-Rossi, Jessica ^{[1
,2
,14
,16
]}

机构：

[1] INSERM, UMR Genom Fonct Tumeurs Solides 674, IUH, F-75010 Paris, France

[2] Univ Paris 05, Labex Immunooncol, Sorbonne Paris Cite, Fac Med, Paris, France

[3] Henri Mondor Univ Hosp, AP HP, Dept Pathol, F-94000 Creteil, France

[4] Univ Paris Est Creteil Val de Marne, UPEC, Paris, France

[5] Antoine Beclere Univ Hosp, AP HP, Dept Pediat, Clamart, France

[6] Univ Paris 11, Paris, France

[7] Antoine Beclere Univ Hosp, AP HP, Dept Surg, Clamart, France

[8] Antoine Beclere Univ Hosp, AP HP, Dept Pathol, Clamart, France

[9] Kings Coll London, Inst Liver Studies, London WC2R 2LS, England

[10] Beaujon Univ Hosp, AP HP, Dept Pathol, Clichy, France

[11] Univ Hosp, Dept Pathol, Ghent, Belgium

[12] Univ Basel Hosp, Dept Pathol, CH-4031 Basel, Switzerland

[13] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, Groningen, Netherlands

[14] Pellegrin Univ Hosp, Dept Pathol, Bordeaux, France

[15] Univ Bordeaux Segalen, GREF Inserm U1053, Bordeaux, France

[16] Hop Europeen Georges Pompidou, AP HP, F-75015 Paris, France

来源：

JOURNAL OF HEPATOLOGY | 2013年 / 58卷 / 02期

关键词：

Carcinogenesis; Hepatocellular carcinoma; Glycolysis; Fatty acid synthesis; Metabolism; Glycogen storage disease; Hepatocellular adenoma; FATTY-ACID SYNTHASE; SUBTYPE CLASSIFICATION; SOMATIC MUTATIONS; CANCER; LIVER; INACTIVATION; METABOLISM; MANAGEMENT; PATHWAYS; GENETICS;

D O I：

10.1016/j.jhep.2012.09.030

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Background & Aims: Hepatocellular adenomas (HCA) are benign liver tumors mainly related to oral contraception and classified into 4 molecular subgroups: inflammatory (IHCA), HNF1A-inactivated (H-HCA), beta-catenin-activated (bHCA) or unclassified (UHCA). Glycogen storage disease type I (GSD) is a rare hereditary metabolic disease that predisposes to HCA development. The aim of our study was to characterize the molecular profile of GSD-associated HCA. Methods: We characterized a series of 25 HCAs developed in 15 patients with GSD by gene expression and DNA sequence of HNF1A, CTNNB1, IL6ST, GNAS, and STAT3 genes. Moreover, we searched for glycolysis, gluconeogenesis, and fatty acid synthesis alterations in GSD non-tumor livers and compared our results to those observed in a series of sporadic H-HCA and various non-GSD liver samples. Results: GSD adenomas were classified as IHCA (52%) mutated for IL6ST or GNAS, bHCA (28%) or UHCA (20%). In contrast, no HNF1A inactivation was observed, showing a different molecular subtype distribution in GSD-associated HCA from that observed in sporadic HCA (p = 0.0008). In non-tumor GSD liver samples, we identified glycolysis and fatty acid synthesis activation with gluconeogenesis repression. Interestingly, this gene expression profile was similar to that observed in sporadic H-HCA. Conclusions: Our study showed a particular molecular profile in GSD-related HCA characterized by a lack of HNF1A inactivation. This exclusion could be explained by similar metabolic defects observed with HNF1A inactivation and glucose-6-phosphatase deficiency. Inversely, the high frequency of beta-catenin mutations could be related to the increased frequency of malignant transformation in hepatocellular carcinoma. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：350 / 357

页数：8

共 36 条

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