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

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 14; pp. 15256 - 15260
• Main Authors: Herold, Natalie, Schmolling, Johanna, Ernst, Corinna, Ataseven, Beyhan, Blümcke, Britta, Schömig‐Markiefka, Birgid, Heikaus, Sebastian, Göhring, Uwe‐Jochen, Engel, Christoph, Lampe, Björn, Rhiem, Kerstin, Harter, Philipp, Hauke, Jan, Schmutzler, Rita K., Hahnen, Eric
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2023; John Wiley and Sons Inc; Wiley
• Subjects: Age; BRCA mutations; Breast cancer; Brief Communication; Cancer Risk Factors; Clinical Cancer Research; DNA Helicases - genetics; Female; Genes; Genetic Predisposition to Disease; Genetic testing; Genotype & phenotype; Germ Cells; Germ-Line Mutation; Gynecological Oncology; Hereditary Cancer; Histology; Humans; Molecular Genetics; Mutation; Nuclear Proteins - genetics; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Patients; SCCOHT; SMARCA4; Transcription Factors - genetics; Tumors; Womens health; BRCA mutations; ovarian cancer; hereditary cancer; SCCOHT; cancer risk factors; gynecological oncology; SMARCA4
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.6214

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.