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

被引：0

作者：

Soukupova, Jana ^{[1
,2
]}

Stastna, Barbora ^{[1
,2
,3
,4
]}

Kanwal, Madiha ^{[3
]}

Hojny, Jan ^{[2
,5
]}

Zemankova, Petra ^{[1
,2
,6
]}

Borecka, Marianna ^{[1
,2
]}

Cerna, Leona ^{[7
]}

Cerna, Marta ^{[1
,2
]}

Cerna, Monika ^{[8
]}

Curtisova, Vaclava ^{[9
]}

Dolezalova, Tatana ^{[1
,2
]}

Duskova, Petra ^{[10
]}

Foretova, Lenka ^{[11
]}

Havranek, Ondrej ^{[2
,12
,13
]}

Horackova, Klara ^{[1
,2
]}

Hovhannisyan, Milena ^{[1
,2
]}

Hruskova, Lucie ^{[14
]}

Chvojka, Stepan ^{[7
]}

Janatova, Marketa ^{[1
,2
]}

Janikova, Maria ^{[9
]}

Jelinkova, Sandra ^{[1
,2
]}

Just, Pavel ^{[1
,2
]}

Kalousova, Marta ^{[1
,2
]}

Kleiblova, Petra ^{[1
,2
,12
]}

Kosarova, Marcela ^{[15
]}

Koudova, Monika ^{[7
]}

Kral, Jan ^{[1
,2
]}

Krausova, Michaela ^{[2
,5
]}

Krutilkova, Vera ^{[16
]}

Machackova, Eva ^{[11
]}

Matejkova, Katerina ^{[1
,2
,17
]}

Michalovska, Renata ^{[14
]}

Nehasil, Petr ^{[1
,2
,6
,18
]}

Nemcova, Barbora ^{[1
,2
]}

Novotny, Jan ^{[2
,12
,19
]}

Palek, Matous ^{[3
]}

Pesek, Pavel ^{[1
,2
]}

Safarikova, Marketa ^{[1
,2
]}

Scheinost, Ondrej ^{[10
]}

Springer, Drahomira ^{[1
,2
]}

Stolarova, Lenka ^{[3
]}

Stranecky, Viktor ^{[2
,18
]}

Subrt, Ivan ^{[8
]}

Tavandzis, Spiros ^{[16
]}

Tureckova, Eva ^{[1
,2
]}

Vesela, Kamila ^{[2
,12
]}

Vlckova, Zdenka ^{[14
]}

Vocka, Michal ^{[2
,20
]}

Zima, Tomas ^{[1
,2
]}

Macurek, Libor ^{[3
]}

机构：

[1] Charles Univ Prague, Inst Med Biochem, Fac Med 1, Inst Med Biochem & Lab Diagnost, Katerinska 32, Prague 12108, Czech Republic

[2] Gen Univ Hosp Prague, Katerinska 32, Prague 12108, Czech Republic

[3] Czech Acad Sci, Inst Mol Genet, Lab Canc Cell Biol, Videnska 1034, Prague 14220, Czech Republic

[4] Charles Univ Prague, Fac Sci, Dept Biochem, Prague, Czech Republic

[5] Charles Univ Prague, Inst Pathol, Fac Med 1, Prague, Czech Republic

[6] Charles Univ Prague, Inst Pathol Physiol, Fac Med 1, Prague, Czech Republic

[7] Ctr Med Genet & Reprod Med, GENNET, Prague, Czech Republic

[8] Univ Hosp Plzen, Inst Med Genet, Plzen, Czech Republic

[9] Palacky Univ, Univ Hosp Olomouc, Fac Med & Dent, Dept Med Genet, Olomouc, Czech Republic

[10] Hosp Ceske Budejovice, Ceske Budejovice, Czech Republic

[11] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic

[12] Charles Univ Prague, Inst Biol & Med Genet, Fac Med 1, Prague, Czech Republic

[13] Charles Univ Prague, Fac Med 1, BIOCEV, Vestec, Czech Republic

[14] GHC Genet, Dept Med Genet, Prague, Czech Republic

[15] Pronatal, Dept Med Genet, Prague, Czech Republic

[16] AGEL Res & Training Inst, Dept Med Genet, AGEL Labs, Novy Jicin, Czech Republic

[17] Charles Univ Prague, Fac Sci, Dept Genet & Microbiol, Prague, Czech Republic

[18] Charles Univ Prague, Fac Med 1, Dept Paediat & Inherited Metab Disorders, Prague, Czech Republic

[19] Inst Clin & Expt Med, Prague, Czech Republic

[20] Charles Univ Prague, Fac Med 1, Dept Oncol, Prague, Czech Republic

来源：

CANCER MEDICINE | 2024年 / 13卷 / 16期

关键词：

breast cancer; Fanconi anemia complementation group G; functional analysis; germline genetic testing; hereditary tumors; ovarian cancer; ANEMIA; ASSOCIATION; REPAIR;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：9

共 15 条

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