Breast (Jun 2024)
A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition
- Petra Zemankova,
- Marta Cerna,
- Klara Horackova,
- Corinna Ernst,
- Jana Soukupova,
- Marianna Borecka,
- Britta Blümcke,
- Leona Cerna,
- Monika Cerna,
- Vaclava Curtisova,
- Tatana Dolezalova,
- Petra Duskova,
- Lenka Dvorakova,
- Lenka Foretova,
- Ondrej Havranek,
- Jan Hauke,
- Eric Hahnen,
- Miloslava Hodulova,
- Milena Hovhannisyan,
- Lucie Hruskova,
- Marketa Janatova,
- Maria Janikova,
- Sandra Jelinkova,
- Pavel Just,
- Marcela Kosarova,
- Monika Koudova,
- Vera Krutilkova,
- Eva Machackova,
- Katerina Matejkova,
- Renata Michalovska,
- Adela Misove,
- Petr Nehasil,
- Barbora Nemcova,
- Jan Novotny,
- Ales Panczak,
- Pavel Pesek,
- Ondrej Scheinost,
- Drahomira Springer,
- Barbora Stastna,
- Viktor Stranecky,
- Ivan Subrt,
- Spiros Tavandzis,
- Eva Tureckova,
- Kamila Vesela,
- Zdenka Vlckova,
- Michal Vocka,
- Barbara Wappenschmidt,
- Tomas Zima,
- Zdenek Kleibl,
- Petra Kleiblova
Affiliations
- Petra Zemankova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; Institute of Pathological Physiology, First Faculty of Medicine, Charles University, 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
- Klara Horackova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- Corinna Ernst
- Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
- Jana Soukupova
- 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
- Britta Blümcke
- Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
- Leona Cerna
- GENNET, Prague, Czech Republic
- Monika Cerna
- Institute of Medical Genetics, University Hospital Pilsen, Pilsen, Czech Republic
- Vaclava Curtisova
- Department of Medical Genetics, University Hospital Olomouc, Faculty of Medicine and Dentistry, 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 Dvorakova
- Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, 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; BIOCEV, First Faculty of Medicine, Charles University, Prague, Czech Republic
- Jan Hauke
- Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
- Eric Hahnen
- Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
- Miloslava Hodulova
- GENNET, 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
- GHC Genetics, 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, University Hospital Olomouc, Faculty of Medicine and Dentistry, 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
- Marcela Kosarova
- Pronatal, Prague, Czech Republic
- Monika Koudova
- GENNET, 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; Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic
- Renata Michalovska
- GHC Genetics, Prague, Czech Republic
- Adela Misove
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, 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; Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Pediatrics and Inherited Metabolic Disorders, 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
- Ales Panczak
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 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
- 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
- Barbora Stastna
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic
- Viktor Stranecky
- Department of Pediatrics 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
- 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
- Barbara Wappenschmidt
- Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
- Tomas Zima
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 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; Institute of Pathological Physiology, First Faculty of Medicine, Charles University, 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; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; Corresponding author. Laboratory of Oncogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Na Bojisti 1660/3, Prague 2, 128 00, Czech Republic.
- Journal volume & issue
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Vol. 75
p. 103721
Abstract
Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.Tyr337PhefsTer37).The variant was found in 21/10,204 (0.21%) Czech FBC patients compared to 1/3250 (0.03%) controls (p = 0.04) and in 4/3639 (0.11%) FBC patients from an independent German dataset. In addition, we found this variant in 5/2966 (0.17%) Czech (but none of the 443 German) ovarian cancer patients, three of whom developed early-onset tumors.Based on these observations, we classified this variant as likely pathogenic.
