| Written | 2006-03 | Jessica Zucman-Rossi |
| Inserm U674, Génomique Fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, 75010 Paris, France |
| Identity |
| Other names | Familial hepatic adenomas |
| Atlas_Id | 10130 |
| Genes implicated in | HNF1A |
| 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 |
| 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. |
| Gene Name | HNF1A (hepatocyte nuclear factor 1 alpha) |
| Alias | TCF1, LFB1, M57732, MODY3 |
| Location | 12q24.31 |
| DNA/RNA | |
| Description | 10 coding exons |
| Protein | |
| Description | hepatocyte nuclear factor 1 alpha, HNF1A |
| Function | transcription factor |
| Homology | homeodomain, pou family |
| Mutations | |
| 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 |
| 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. |
| Chiche L, Dao T, Salamé E, Galais MP, Bouvard N, Schmutz G, Rousselot P, Bioulac-Sage P, Ségol P, Gignoux M |
| Annals of surgery. 2000 ; 231 (1) : 74-81. |
| 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. |
| Reznik Y, Dao T, Coutant R, Chiche L, Jeannot E, Clauin S, Rousselot P, Fabre M, Oberti F, Fatome A, Zucman-Rossi J, Bellanne-Chantelot C |
| 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) |
| Yamagata K, Oda N, Kaisaki PJ, Menzel S, Furuta H, Vaxillaire M, Southam L, Cox RD, Lathrop GM, Boriraj VV, Chen X, Cox NJ, Oda Y, Yano H, Le Beau MM, Yamada S, Nishigori H, Takeda J, Fajans SS, Hattersley AT, Iwasaki N, Hansen T, Pedersen O, Polonsky KS, Bell GI |
| 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 |
| Citation |
| This paper should be referenced as such : |
| Zucman-Rossi, J |
| Familial liver adenomatosis |
| Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):208-209. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Tumors/FamLiverAdenomID10130.html |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:24:19 CEST 2017 |
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