A comprehensive study evaluating germline <scp><i>FANCG</i></scp> variants in predisposition to breast and ovarian cancer-Reference-Cited by-同舟云学术

A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer

Published:2024-08 Issue:16 Volume:13 Page:
ISSN:2045-7634
Container-title:Cancer Medicine
language:en
Short-container-title:Cancer Medicine

Author:

Soukupova Jana¹,Stastna Barbora¹²³,Kanwal Madiha²,Hojny Jan⁴,Zemankova Petra¹⁵,Borecka Marianna¹,Cerna Leona⁶,Cerna Marta¹,Cerna Monika⁷,Curtisova Vaclava⁸,Dolezalova Tatana¹,Duskova Petra⁹,Foretova Lenka¹⁰,Havranek Ondrej¹¹¹²,Horackova Klara¹,Hovhannisyan Milena¹,Hruskova Lucie¹³,Chvojka Stepan⁶,Janatova Marketa¹,Janikova Maria⁸,Jelinkova Sandra¹,Just Pavel¹,Kalousova Marta¹,Kleiblova Petra¹¹¹,Kosarova Marcela¹⁴,Koudova Monika⁶,Kral Jan¹,Krausova Michaela⁴,Krutilkova Vera¹⁵,Machackova Eva¹⁰,Matejkova Katerina¹¹⁶,Michalovska Renata¹³,Nehasil Petr¹⁵¹⁷,Nemcova Barbora¹,Novotny Jan¹¹¹⁸,Palek Matous²,Pesek Pavel¹,Safarikova Marketa¹,Scheinost Ondrej⁹,Springer Drahomira¹,Stolarova Lenka²,Stranecky Viktor¹⁷,Subrt Ivan⁷,Tavandzis Spiros¹⁵,Tureckova Eva¹,Vesela Kamila¹¹,Vlckova Zdenka¹³,Vocka Michal¹⁹,Zima Tomas¹,Macurek Libor²^ORCID,Kleibl Zdenek¹⁵^ORCID,

Affiliation:

1. Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic

2. Laboratory of Cancer Cell Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

3. Department of Biochemistry, Faculty of Science Charles University Prague Czech Republic

4. Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic

5. Institute of Pathological Physiology, First Faculty of Medicine, Charles University Prague Czech Republic

6. Centre for Medical Genetics and Reproductive Medicine, GENNET Prague Czech Republic

7. Institute of Medical Genetics, University Hospital Pilsen Pilsen Czech Republic

8. Department of Medical Genetics Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc Czech Republic

9. Hospital Ceske Budejovice Ceske Budejovice Czech Republic

10. Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

11. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague Prague Czech Republic

12. BIOCEV, First Faculty of Medicine Charles University Vestec Czech Republic

13. Department of Medical Genetics GHC Genetics Prague Czech Republic

14. Department of Medical Genetics Pronatal Prague Czech Republic

15. Department of Medical Genetics, AGEL Laboratories AGEL Research and Training Institute Novy Jicin Czech Republic

16. Department of Genetics and Microbiology, Faculty of Science Charles University in Prague Prague Czech Republic

17. Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech Republic

18. Institute for Clinical and Experimental Medicine Prague Czech Republic

19. Department of Oncology, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech Republic

Abstract

AbstractBackgroundMonoallelic 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.MethodsHere, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk.ResultsThe 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.ConclusionOur study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.

Funder

Ministerstvo Školství, Mládeže a Tělovýchovy

Ministerstvo Zdravotnictví Ceské Republiky

Grantová Agentura, Univerzita Karlova

Publisher

Wiley

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.70103

Reference15 articles.

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2. Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets

3. Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients

4. K63-linked ubiquitination of FANCG is required for its association with the Rap80-BRCA1 complex to modulate homologous recombination repair of DNA interstand crosslinks

5. Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology