Format

Send to

Choose Destination
Fam Cancer. 2017 Jul;16(3):395-399. doi: 10.1007/s10689-016-9957-6.

The hereditary nature of small cell carcinoma of the ovary, hypercalcemic type: two new familial cases.

Author information

1
Department of Human Genetics, McGill University, Montreal, QC, Canada.
2
Lady Davis Institute and Segal Cancer Center, Jewish General Hospital, 3755 Cote Ste Catherine Road, Montreal, QC, H3T 1E2, Canada.
3
College of Medicine at Peoria, University of Illinois, Peoria, IL, USA.
4
Illinois Cancer Care, Peoria, IL, USA.
5
Department of Pathology, McGill University, Montreal, QC, Canada.
6
Duke University Medical Center, Durham, NC, USA.
7
Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
8
Institute of Neuropathology, University Hospital Münster, Münster, Germany.
9
Department of Human Genetics, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca.
10
Lady Davis Institute and Segal Cancer Center, Jewish General Hospital, 3755 Cote Ste Catherine Road, Montreal, QC, H3T 1E2, Canada. william.foulkes@mcgill.ca.
11
Department of Medical Genetics and Cancer Research Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada. william.foulkes@mcgill.ca.

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.

KEYWORDS:

Hereditary; Mutation; Ovarian cancer; Rhabdoid; SCCOHT; SMARCA4

PMID:
27866340
PMCID:
PMC5487815
DOI:
10.1007/s10689-016-9957-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center