title: The co-occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome.
abstract: The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Pleuropulmonary blastoma is the most frequent lesion seen in this syndrome. Thyroid abnormalities are also a common finding, essentially concerning multinodular goiter. However, differentiated thyroid carcinoma is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 RNase IIIb catalytic domain in several tumor types, including ovarian Sertoli-Leydig cell tumors. We report two cases of differentiated thyroid carcinoma associated with ovarian Sertoli-Leydig cell tumor and with a heterozygous DICER1 gene mutation, occurring in two unrelated young girls without pleuropulmonary blastoma. Both thyroid carcinomas showed an E1813 mutation in exon 25 while the ovarian tumors harboured a somatic mutation in E1705 in exon 24 and a D1709 mutation in exon 25. Our observations confirm that the occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome. We contend that the possibility of a relationship between sporadic thyroid carcinoma in young patients and somatic DICER1 gene mutation needs further investigation.
authors.affiliation: Department of Pathology, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Université Lyon I, 103 Grande rue de la Croix Rousse, 69004, Lyon, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Durieux
authors.affiliation: Biochimie Biologie Moléculaire, Hospices Civils de Lyon, Centre hospitalier Lyon Sud, 69495 Pierre Bénite, Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Descotes
authors.affiliation: Department of Pathology, Hospices Civils de Lyon, Centre hospitalier Lyon Sud, Université Lyon I, 69495 Pierre Bénite, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Mauduit
authors.affiliation: Department of Pathology, Hospices Civils de Lyon, Centre hospitalier Lyon Sud, Université Lyon I, 69495 Pierre Bénite, Lyon, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin
authors.affiliation: Department of Pathology, CHRU Tours, 37044 Cedex 9, Tours, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Guyetant
authors.affiliation: Department of Pathology, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Université Lyon I, 103 Grande rue de la Croix Rousse, 69004, Lyon, France. mojgan.devouassoux@chu-lyon.fr.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
mesh_terms: D000293:Adolescent; D002648:Child; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D018202:Pulmonary Blastoma / Q000473:pathology; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism*; D018310:Sertoli-Leydig Cell Tumor / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER-1; Pleuropulmonary blastoma; Sertoli-Leydig cell tumor; Thyroid carcinoma; familial neoplasia