A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer
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....
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2024-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70103 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jana Soukupova |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a729e3f3d4b64ad89ec8fbe20e608bd3 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-a729e3f3d4b64ad89ec8fbe20e608bd32024-11-26T10:12:30ZengWileyCancer Medicine2045-76342024-08-011316n/an/a10.1002/cam4.70103A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancerJana Soukupova0Barbora Stastna1Madiha Kanwal2Jan Hojny3Petra Zemankova4Marianna Borecka5Leona Cerna6Marta Cerna7Monika Cerna8Vaclava Curtisova9Tatana Dolezalova10Petra Duskova11Lenka Foretova12Ondrej Havranek13Klara Horackova14Milena Hovhannisyan15Lucie Hruskova16Stepan Chvojka17Marketa Janatova18Maria Janikova19Sandra Jelinkova20Pavel Just21Marta Kalousova22Petra Kleiblova23Marcela Kosarova24Monika Koudova25Jan Kral26Michaela Krausova27Vera Krutilkova28Eva Machackova29Katerina Matejkova30Renata Michalovska31Petr Nehasil32Barbora Nemcova33Jan Novotny34Matous Palek35Pavel Pesek36Marketa Safarikova37Ondrej Scheinost38Drahomira Springer39Lenka Stolarova40Viktor Stranecky41Ivan Subrt42Spiros Tavandzis43Eva Tureckova44Kamila Vesela45Zdenka Vlckova46Michal Vocka47Tomas Zima48Libor Macurek49Zdenek Kleibl50the CZECANCA consortiumInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicLaboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech RepublicInstitute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicCentre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Genetics, University Hospital Pilsen Pilsen Czech RepublicDepartment of Medical Genetics Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicHospital Ceske Budejovice Ceske Budejovice Czech RepublicDepartment of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicDepartment of Medical Genetics GHC Genetics Prague Czech RepublicCentre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicDepartment of Medical Genetics Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicDepartment of Medical Genetics Pronatal Prague Czech RepublicCentre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicDepartment of Medical Genetics, AGEL Laboratories AGEL Research and Training Institute Novy Jicin Czech RepublicDepartment of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicDepartment of Medical Genetics GHC Genetics Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicLaboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicHospital Ceske Budejovice Ceske Budejovice Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicLaboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech RepublicDepartment of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Genetics, University Hospital Pilsen Pilsen Czech RepublicDepartment of Medical Genetics, AGEL Laboratories AGEL Research and Training Institute Novy Jicin Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicDepartment of Medical Genetics GHC Genetics Prague Czech RepublicDepartment of Oncology, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicLaboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech RepublicAbstract 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.https://doi.org/10.1002/cam4.70103breast cancerFanconi anemia complementation group Gfunctional analysisgermline genetic testinghereditary tumorsovarian cancer |
| spellingShingle | 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 A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer Cancer Medicine breast cancer Fanconi anemia complementation group G functional analysis germline genetic testing hereditary tumors ovarian cancer |
| title | A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer |
| title_full | A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer |
| title_fullStr | A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer |
| title_full_unstemmed | A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer |
| title_short | A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer |
| title_sort | comprehensive study evaluating germline fancg variants in predisposition to breast and ovarian cancer |
| topic | breast cancer Fanconi anemia complementation group G functional analysis germline genetic testing hereditary tumors ovarian cancer |
| url | https://doi.org/10.1002/cam4.70103 |
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