Pathogenic germline variants in SMARCA4 and further cancer predisposition genes in early onset ovarian cancer

Natalie Herold; Johanna Schmolling; Corinna Ernst; Beyhan Ataseven; Britta Blümcke; Birgid Schömig-Markiefka; Sebastian Heikaus; Uwe-Jochen Göhring; Christoph Engel; Björn Lampe; Kerstin Rhiem; Philipp Harter; Jan Hauke; Rita K Schmutzler; Eric Hahnen

doi:10.1002/cam4.6214

Pathogenic germline variants in SMARCA4 and further cancer predisposition genes in early onset ovarian cancer

Cancer Med. 2023 Jul;12(14):15256-15260. doi: 10.1002/cam4.6214. Epub 2023 Jun 22.

Authors

Affiliations

¹ Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany.
² Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen, Germany.
³ Medical School and University Medical Center East Westphalia-Lippe, Klinikum Lippe, Academic Department of Gynecology, Gynecologic Oncology and Obstetrics, Bielefeld University, Detmold, Germany.
⁴ Institute of Pathology, University Hospital Cologne, Cologne, Germany.
⁵ Department of Pathology, Kliniken Essen-Mitte (KEM) Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.
⁶ Department of Gynecology and Obstetrics, Johanniter Krankenhaus, Bonn, Germany.
⁷ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁸ Department of Gynecology and Obstetrics, Diakonie Kaiserswerth, Düsseldorf, Germany.

Abstract

To assess the role of germline pathogenic variants (PVs) in SMARCA4 and further established ovarian cancer (OC) predisposition genes in early onset OC, we investigated a clinical cohort of 206 unrelated OC index patients with an age at diagnosis of OC ≤40 years using an extended panel of 24 (candidate) cancer predisposition genes. PVs in established OC predisposition genes were most frequent in patients with high grade serous OC (21/62, 33.9%), comparatively rare in patients with epithelial OC other than high grade serous (5/74, 6.8%) or borderline ovarian tumours (2/39, 5.1%) and absent in mucinous OC (0/27). We demonstrate that germline PVs in SMARCA4 unlikely predispose for early onset OC other than SCCOHT.

Keywords: SMARCA4; BRCA mutations; SCCOHT; cancer risk factors; gynecological oncology; hereditary cancer; ovarian cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Helicases / genetics
Female
Genetic Predisposition to Disease
Germ Cells
Germ-Line Mutation*
Humans
Nuclear Proteins / genetics
Ovarian Neoplasms* / genetics
Ovarian Neoplasms* / pathology
Transcription Factors / genetics

Substances

SMARCA4 protein, human
DNA Helicases
Nuclear Proteins
Transcription Factors