Cancers (Apr 2020)
Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer
- Klara Lhotova,
- Lenka Stolarova,
- Petra Zemankova,
- Michal Vocka,
- Marketa Janatova,
- Marianna Borecka,
- Marta Cerna,
- Sandra Jelinkova,
- Jan Kral,
- Zuzana Volkova,
- Marketa Urbanova,
- Petra Kleiblova,
- Eva Machackova,
- Lenka Foretova,
- Jana Hazova,
- Petra Vasickova,
- Filip Lhota,
- Monika Koudova,
- Leona Cerna,
- Spiros Tavandzis,
- Jana Indrakova,
- Lucie Hruskova,
- Marcela Kosarova,
- Radek Vrtel,
- Viktor Stranecky,
- Stanislav Kmoch,
- Michal Zikan,
- Libor Macurek,
- Zdenek Kleibl,
- Jana Soukupova
Affiliations
- Klara Lhotova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Lenka Stolarova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Petra Zemankova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Michal Vocka
- Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic
- Marketa Janatova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Marianna Borecka
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Marta Cerna
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Sandra Jelinkova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Jan Kral
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Zuzana Volkova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Marketa Urbanova
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic
- Petra Kleiblova
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic
- Eva Machackova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic
- Lenka Foretova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic
- Jana Hazova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic
- Petra Vasickova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic
- Filip Lhota
- Department of Medical Genetics, Centre for Medical Genetics and Reproductive Medicine, Gennet, 170 00 Prague, Czech Republic
- Monika Koudova
- Department of Medical Genetics, Centre for Medical Genetics and Reproductive Medicine, Gennet, 170 00 Prague, Czech Republic
- Leona Cerna
- Department of Medical Genetics, Centre for Medical Genetics and Reproductive Medicine, Gennet, 170 00 Prague, Czech Republic
- Spiros Tavandzis
- Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, 741 01 Novy Jicin, Czech Republic
- Jana Indrakova
- Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, 741 01 Novy Jicin, Czech Republic
- Lucie Hruskova
- Department of Medical Genetics, GHC Genetics, 110 00 Prague, Czech Republic
- Marcela Kosarova
- Department of Medical Genetics, Pronatal, 147 00 Prague, Czech Republic
- Radek Vrtel
- Department of Medical Genetics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University Olomouc, 779 00 Olomouc, Czech Republic
- Viktor Stranecky
- Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Stanislav Kmoch
- Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic
- Michal Zikan
- Department of Gynecology and Obstetrics, Hospital Na Bulovce and First Faculty of Medicine, Charles University, 180 81 Prague, Czech Republic
- Libor Macurek
- Laboratory of Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
- Zdenek Kleibl
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- Jana Soukupova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic
- DOI
- https://doi.org/10.3390/cancers12040956
- Journal volume & issue
-
Vol. 12,
no. 4
p. 956
Abstract
Ovarian cancer (OC) is the deadliest gynecologic malignancy with a substantial proportion of hereditary cases and a frequent association with breast cancer (BC). Genetic testing facilitates treatment and preventive strategies reducing OC mortality in mutation carriers. However, the prevalence of germline mutations varies among populations and many rarely mutated OC predisposition genes remain to be identified. We aimed to analyze 219 genes in 1333 Czech OC patients and 2278 population-matched controls using next-generation sequencing. We revealed germline mutations in 18 OC/BC predisposition genes in 32.0% of patients and in 2.5% of controls. Mutations in BRCA1/BRCA2, RAD51C/RAD51D, BARD1, and mismatch repair genes conferred high OC risk (OR > 5). Mutations in BRIP1 and NBN were associated with moderate risk (both OR = 3.5). BRCA1/2 mutations dominated in almost all clinicopathological subgroups including sporadic borderline tumors of ovary (BTO). Analysis of remaining 201 genes revealed somatic mosaics in PPM1D and germline mutations in SHPRH and NAT1 associating with a high/moderate OC risk significantly; however, further studies are warranted to delineate their contribution to OC development in other populations. Our findings demonstrate the high proportion of patients with hereditary OC in Slavic population justifying genetic testing in all patients with OC, including BTO.
Keywords