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Familial liver adenomatosis

Written2006-03Jessica Zucman-Rossi
Inserm U674, Génomique Fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, 75010 Paris, France

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Other namesFamilial hepatic adenomas
Atlas_Id 10130
Genes implicated inHNF1A  
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


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.
Gene NameHNF1A (HNF1 homeobox A)
Alias TCF1, LFB1, M57732, MODY3
Location 12q24.31
Description 10 coding exons
Description hepatocyte nuclear factor 1 alpha, HNF1A
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.


Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.
Bacq Y, Jacquemin E, Balabaud C, Jeannot E, Scotto B, Branchereau S, Laurent C, Bourlier P, Pariente D, de Muret A, Fabre M, Bioulac-Sage P, Zucman-Rossi J
Gastroenterology. 2003 ; 125 (5) : 1470-1475.
PMID 14598263
Bi-allelic inactivation of TCF1 in hepatic adenomas.
Bluteau O, Jeannot E, Bioulac-Sage P, Marqués JM, Blanc JF, Bui H, Beaudoin JC, Franco D, Balabaud C, Laurent-Puig P, Zucman-Rossi J
Nature genetics. 2002 ; 32 (2) : 312-315.
PMID 12355088
Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature.
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PMID 10636105
Familial liver-cell adenomas and diabetes mellitus.
Foster JH, Donohue TA, Berman MM
The New England journal of medicine. 1978 ; 299 (5) : 239-241.
PMID 207987
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.
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The Journal of clinical endocrinology and metabolism. 2004 ; 89 (3) : 1476-1480.
PMID 15001650
Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)
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Nature. 1996 ; 384 (6608) : 455-458.
PMID 8945470
Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.
Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, Bacq Y, Leteurtre E, Paradis V, Michalak S, Wendum D, Chiche L, Fabre M, Mellottee L, Laurent C, Partensky C, Castaing D, Zafrani ES, Laurent-Puig P, Balabaud C, Bioulac-Sage P
Hepatology (Baltimore, Md.). 2006 ; 43 (3) : 515-524.
PMID 16496320


This paper should be referenced as such :
Zucman-Rossi, J
Familial liver adenomatosis
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):208-209.
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