1. ¹Inserm U434, 27 rue Juliette Dodu, 75010 Paris, France
2. ²CEPH Fondation Jean Dausset, 27 rue Juliette Dodu, 75010 Paris, France
3. ³Service d'Anatomopathologie, Institut Curie, 26 rue d'Ulm, 75005 Paris, France
4. ⁴Service de Gynécologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 20 rue de Leblanc, 75015 Paris, France
5. ⁵Service d'anatomopathologie Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 20 rue Leblanc, 75015 Paris, France
6. ⁶Inserm U490, Laboratoire de Toxicologie Moléculaire, 45 rue des Saints Pères, 75006 Paris, France

Correspondence: J Zucman-Rossi, E-mail: zucman@cephb.fr

Received 10 February 2004; Revised 15 June 2004; Accepted 15 June 2004; Published online 23 August 2004.

Abstract

TCF1 (transcription factor 1) encoding hepatocyte nuclear factor 1 (HNF1) is mutated in 50% of liver cell adenomas, a benign tumor closely associated with oral contraceptive use. These genetic alterations inactivate both alleles, leading to the absence of wild-type HNF1 expression in liver cell adenomas. To search for a role of HNF1 in other hormone-related neoplasias, we screened for HNF1 mutations in a series of 36 endometrial carcinomas, 29 breast carcinomas and 20 ovarian epithelial tumors. HNF1 mutations were identified in 4/36 (11%) of endometrial tumors. No mutation was found in ovarian and breast tumors. HNF1 mutations were somatic in all cases, monoallelic in three cases and biallelic in one case. These results suggest that HNF1 may contribute to endometrial carcinogenesis through complete HNF1 inactivation like in liver cell adenoma or by haploinsufficiency like in MSI-H colorectal cancer.