title: Germline and Somatic DICER1 Mutations in a Well-Differentiated Fetal Adenocarcinoma of the Lung.
abstract: Germ-line DICER1 mutations predispose to a distinctive tumour predisposition syndrome, the DICER1 syndrome, which is associated with a spectrum of rare mainly childhood-onset tumours. In 2014, a case of well-differentiated fetal adenocarcinoma of the lung (WDFA) was reported in a 16-year-old germ-line DICER1 mutation carrier. Here we report our finding of a characteristic somatic DICER1 RNase IIIb c.5127T>A (p.Asp1709Glu) missense mutation within the WDFA, confirmed using laser capture microscopy. The child has a personal history consistent with the DICER1 syndrome: she developed a multinodular goitre at age 14 years and an ovarian Sertoli-Leydig cell tumour at age 16 years, each of which were found to harbour a somatic DICER1 RNase IIIb missense mutation. The identification of two DICER1 "hits" in the WDFA strongly suggests that WDFA is a rare, previously-unrecognised manifestation of DICER1 syndrome.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Leanne
authors.initials: L
authors.lastname: de Kock
authors.affiliation: Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Ismaël
authors.initials: I
authors.lastname: Bah
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yingchen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Xie
authors.affiliation: Minneapolis, MN, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Priest
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada; Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada. Electronic address: william.foulkes@mcgill.ca.
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000293:Adolescent; D002454:Cell Differentiation / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D043244:Ribonuclease III / Q000235:genetics*
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER1; Laser capture microdissection; Mutation; Well-differentiated fetal adenocarcinoma; β-catenin