title: The hereditary nature of small cell carcinoma of the ovary, hypercalcemic type: two new familial cases.
abstract: Small cell carcinoma of the ovary, hypercalcemic type, (SCCOHT) is the most common undifferentiated ovarian cancer in women aged under 40 years. SCCOHT is a monogenic disease, characterized by germline and somatic SMARCA4 mutations. Recent studies have stressed its morphological and clinical similarity to malignant rhabdoid tumours, which are usually caused by mutations in the related gene, SMARCB1. While familial tumours are rare, the incidence of germline mutations is relatively high, with up to 43% of SCCOHTs and 35% of rhabdoid tumours caused by germline mutations in SMARCA4 and SMARCB1, respectively. We report two new familial cases of SCCOHT. Affected members in both families and the associated tumours were found to carry SMARCA4 germline and somatic mutations, respectively, leading to loss of SMARCA4 protein expression in the tumours. Despite the rarity of familial SCCOHT, the high incidence of germline mutations is important to note, as without a family history of the disease, the hereditary nature of SCCOHT may be missed, especially if the mutation was inherited from the father or acquired de novo. The similarity between SCCOHT and rhabdoid tumours should be recognized, as infant carriers of SMARCA4 mutations may be at risk for these tumours in addition to SCCOHT.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, Canada.|Lady Davis Institute and Segal Cancer Center, Jewish General Hospital, 3755 Cote Ste Catherine Road, Montreal, QC, H3T 1E2, Canada.
authors.forename: Leora
authors.initials: L
authors.lastname: Witkowski
authors.affiliation: College of Medicine at Peoria, University of Illinois, Peoria, IL, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Donini
authors.affiliation: College of Medicine at Peoria, University of Illinois, Peoria, IL, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Byler-Dann
authors.affiliation: Illinois Cancer Care, Peoria, IL, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Knost
authors.affiliation: Department of Pathology, McGill University, Montreal, QC, Canada.
authors.forename: Steffen
authors.initials: S
authors.lastname: Albrecht
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.affiliation: Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca.|Lady Davis Institute and Segal Cancer Center, Jewish General Hospital, 3755 Cote Ste Catherine Road, Montreal, QC, H3T 1E2, Canada. william.foulkes@mcgill.ca.|Department of Medical Genetics and Cancer Research Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada. william.foulkes@mcgill.ca.
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D000328:Adult; D018288:Carcinoma, Small Cell / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006934:Hypercalcemia; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: Hereditary; Mutation; Ovarian cancer; Rhabdoid; SCCOHT; SMARCA4