Cancer Medicine (Aug 2024)
A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer
- Jana Soukupova,
- Barbora Stastna,
- Madiha Kanwal,
- Jan Hojny,
- Petra Zemankova,
- Marianna Borecka,
- Leona Cerna,
- Marta Cerna,
- Monika Cerna,
- Vaclava Curtisova,
- Tatana Dolezalova,
- Petra Duskova,
- Lenka Foretova,
- Ondrej Havranek,
- Klara Horackova,
- Milena Hovhannisyan,
- Lucie Hruskova,
- Stepan Chvojka,
- Marketa Janatova,
- Maria Janikova,
- Sandra Jelinkova,
- Pavel Just,
- Marta Kalousova,
- Petra Kleiblova,
- Marcela Kosarova,
- Monika Koudova,
- Jan Kral,
- Michaela Krausova,
- Vera Krutilkova,
- Eva Machackova,
- Katerina Matejkova,
- Renata Michalovska,
- Petr Nehasil,
- Barbora Nemcova,
- Jan Novotny,
- Matous Palek,
- Pavel Pesek,
- Marketa Safarikova,
- Ondrej Scheinost,
- Drahomira Springer,
- Lenka Stolarova,
- Viktor Stranecky,
- Ivan Subrt,
- Spiros Tavandzis,
- Eva Tureckova,
- Kamila Vesela,
- Zdenka Vlckova,
- Michal Vocka,
- Tomas Zima,
- Libor Macurek,
- Zdenek Kleibl,
- the CZECANCA consortium
Affiliations
- Jana Soukupova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Barbora Stastna
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Madiha Kanwal
- Laboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic
- Jan Hojny
- Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Petra Zemankova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Marianna Borecka
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Leona Cerna
- Centre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech Republic
- Marta Cerna
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Monika Cerna
- Institute of Medical Genetics, University Hospital Pilsen Pilsen Czech Republic
- Vaclava Curtisova
- Department of Medical Genetics Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc Czech Republic
- Tatana Dolezalova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Petra Duskova
- Hospital Ceske Budejovice Ceske Budejovice Czech Republic
- Lenka Foretova
- Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
- Ondrej Havranek
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Klara Horackova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Milena Hovhannisyan
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Lucie Hruskova
- Department of Medical Genetics GHC Genetics Prague Czech Republic
- Stepan Chvojka
- Centre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech Republic
- Marketa Janatova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Maria Janikova
- Department of Medical Genetics Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc Czech Republic
- Sandra Jelinkova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Pavel Just
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Marta Kalousova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Petra Kleiblova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Marcela Kosarova
- Department of Medical Genetics Pronatal Prague Czech Republic
- Monika Koudova
- Centre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech Republic
- Jan Kral
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Michaela Krausova
- Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Vera Krutilkova
- Department of Medical Genetics, AGEL Laboratories AGEL Research and Training Institute Novy Jicin Czech Republic
- Eva Machackova
- Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
- Katerina Matejkova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Renata Michalovska
- Department of Medical Genetics GHC Genetics Prague Czech Republic
- Petr Nehasil
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Barbora Nemcova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Jan Novotny
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Matous Palek
- Laboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic
- Pavel Pesek
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Marketa Safarikova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Ondrej Scheinost
- Hospital Ceske Budejovice Ceske Budejovice Czech Republic
- Drahomira Springer
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Lenka Stolarova
- Laboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic
- Viktor Stranecky
- Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech Republic
- Ivan Subrt
- Institute of Medical Genetics, University Hospital Pilsen Pilsen Czech Republic
- Spiros Tavandzis
- Department of Medical Genetics, AGEL Laboratories AGEL Research and Training Institute Novy Jicin Czech Republic
- Eva Tureckova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Kamila Vesela
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Zdenka Vlckova
- Department of Medical Genetics GHC Genetics Prague Czech Republic
- Michal Vocka
- Department of Oncology, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech Republic
- Tomas Zima
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- Libor Macurek
- Laboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic
- Zdenek Kleibl
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic
- the CZECANCA consortium
- DOI
- https://doi.org/10.1002/cam4.70103
- Journal volume & issue
-
Vol. 13,
no. 16
pp. n/a – n/a
Abstract
Abstract Background Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role of GPVs in 17 other FA genes remains unclear. Methods Here, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk. Results The frequency of truncating GPVs in FANCG did not differ between BC (20/10,204; 0.20%) and OC (8/2966; 0.27%) patients compared to controls (6/3250; 0.18%). In addition, only one out of five tumor samples showed loss‐of‐heterozygosity of the wild‐type FANCG allele. Finally, none of the nine functionally tested rare recurrent missense FANCG variants impaired DNA repair activities (FANCD2 monoubiquitination and FANCD2 foci formation) upon DNA damage, in contrast to all tested FANCG truncations. Conclusion Our study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.
Keywords
- breast cancer
- Fanconi anemia complementation group G
- functional analysis
- germline genetic testing
- hereditary tumors
- ovarian cancer
