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Complete human genomed sequenced
HGNC Gene Fusions Nomenclature
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Familial liver adenomatosis
Inserm U674, Génomique Fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, 75010 Paris, France
Familial liver adenomatosis
Familial hepatic adenomas
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
\/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.
autosomal dominant disorder with low penetrance
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.
Among MODY3 patients only a very small minority will develop liver adenomatosis. Cases of malignant transformation are uncommon.
Patients presenting TCF1\/HNF1a mutated adenomatosis are at risk of tumor hemorrhagic rupture.
Genes involved and Proteins
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.
TCF1, LFB1, M57732, MODY3
10 coding exons
homeodomain, pou family
at least 6 different mutations were found in familial adenomatosis: R229X, R272S, P291fs (2 cases), G55fs, IVS2 +1 G>T
inactivation of the second allele in adenoma tumors is by gene deletion or mutation.
Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.
Bacq Y et al
Bi-allelic inactivation of TCF1 in hepatic adenomas.
Bluteau O et al
Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature.
Chiche L et al
Familial liver-cell adenomas and diabetes mellitus.
Foster JH et al
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
Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3).
Yamagata K et al
Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.
Zucman-Rossi J et al
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