Familial liver adenomatosis

2006-03-01 Jessica Zucman-Rossi Affiliation

Inserm U674, Génomique Fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, 75010 Paris, France

Identity

Name

Alias

Familial hepatic adenomas

Note

Liver adenomatosis is a rare disease defined by the presence of multiple adenomas within an otherwise normal hepatic parenchyma. In 2002, frequent bi-allelic inactivation of TCF1\/HNF-1alpha, was identified in hepatocellular adenomas. In 80% of the cases both mutations were of somatic origin. However, in the remaining cases, one heterozygous germline mutation has been found in patients revealing a relation between liver adenomatosis and maturity-onset diabetes of the young (MODY3). MODY3 is a rare dominantly inherited subtype of non-insulin-dependent diabetes mellitus characterized by early onset, usually before the age of 25, and a primary defect in insulin secretion. In 1996, heterozygous germline mutations of TCF1\/HNF1a have been linked to the occurrence of MODY3 in humans.

Inheritance

autosomal dominant disorder with low penetrance

Omim

142330

Orphanet

- -

Umls

Clinics

Phenotype and clinics

To date, all familial liver adenomatosis cases described are related to TCF1\/HFN1a constitutional mutation. Genotype-phenotype correlation analysis showed that TCF1\/HNF1a benign lesions were steatotic.

Neoplastic risk

Among MODY3 patients only a very small minority will develop liver adenomatosis. Cases of malignant transformation are uncommon.

Evolution

Patients presenting TCF1\/HNF1a mutated adenomatosis are at risk of tumor hemorrhagic rupture.

Genes involved and Proteins

Note

HNF1a is a homeodomain containing transcription factor that is implicated in hepatocyte differentiation and is required for the liver-specific expression of several genes, including β-fibrinogen, albumin and a1-antitrypsin.

Alias

TCF1, LFB1, M57732, MODY3

Description

10 coding exons

Function

transcription factor

Homology

homeodomain, pou family

Germinal

at least 6 different mutations were found in familial adenomatosis: R229X, R272S, P291fs (2 cases), G55fs, IVS2 +1 G>T

Somatic

inactivation of the second allele in adenoma tumors is by gene deletion or mutation.

Bibliography

Pubmed ID	Last Year	Title	Authors
14598263	2003	Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.	Bacq Y et al
12355088	2002	Bi-allelic inactivation of TCF1 in hepatic adenomas.	Bluteau O et al
10636105	2000	Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature.	Chiche L et al
207987	1978	Familial liver-cell adenomas and diabetes mellitus.	Foster JH et al
15001650	2004	Hepatocyte nuclear factor-1 alpha gene inactivation: cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families.	Reznik Y et al
8945470	1996	Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3).	Yamagata K et al
16496320	2006	Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.	Zucman-Rossi J et al