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Article Open Access

Germline multigene panel testing of patients with endometrial cancer

  • Authors:
    • Jan Kral
    • Sandra Jelinkova
    • Petra Zemankova
    • Michal Vocka
    • Marianna Borecka
    • Leona Cerna
    • Marta Cerna
    • Lukas Dostalek
    • Petra Duskova
    • Lenka Foretova
    • Ondrej Havranek
    • Klara Horackova
    • Milena Hovhannisyan
    • Stepan Chvojka
    • Marta Kalousova
    • Marcela Kosarova
    • Monika Koudova
    • Vera Krutilkova
    • Eva Machackova
    • Petr Nehasil
    • Jan Novotny
    • Barbora Otahalova
    • Alena Puchmajerova
    • Marketa Safarikova
    • Jiri Slama
    • Viktor Stranecky
    • Ivan Subrt
    • Spiros Tavandzis
    • Michal Zikan
    • Tomas Zima
    • Jana Soukupova
    • Petra Kleiblova
    • Zdenek Kleibl
    • Marketa Janatova
  • View Affiliations / Copyright

    Affiliations: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic, Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic, Center for Medical Genetics and Reproductive Medicine, Gennet, Prague 170 00, Czech Republic, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic, Laboratory of Molecular Genetics, Hospital Ceske Budejovice, Ceske Budejovice 370 00, Czech Republic, Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno 656 53, Czech Republic, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic, Department of Medical Genetics, Pronatal, Prague 140 00, Czech Republic, Department of Medical Genetics, AGEL Laboratories, AGEL Research and Training Institute, Novy Jicin 741 00, Czech Republic, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 120 00, Czech Republic, Department of Medical Genetics, Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, Pilsen 323 00, Czech Republic, Department of Gynecology and Obstetrics, Bulovka University Hospital and First Faculty of Medicine, Charles University, Prague 180 00, Czech Republic
    Copyright: © Kral et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 216
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    Published online on: April 12, 2023
       https://doi.org/10.3892/ol.2023.13802
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Abstract

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. The present study aimed to determine the frequency of germline pathogenic variants (PV) in patients with EC. In this multicenter retrospective cohort study, germline genetic testing (GGT) was performed in 527 patients with EC using a next generation sequencing panel targeting 226 genes, including 5 Lynch syndrome (LS) and 14 hereditary breast and ovarian cancer (HBOC) predisposition genes, and 207 candidate predisposition genes. Gene‑level risks were calculated using 1,662 population‑matched controls (PMCs). Patients were sub‑categorized to fulfill GGT criteria for LS, HBOC, both or none. A total of 60 patients (11.4%) carried PV in LS (5.1%) and HBOC (6.6%) predisposition genes, including two carriers of double PV. PV in LS genes conferred a significantly higher EC risk [odds ratio (OR), 22.4; 95% CI, 7.8‑64.3; P=1.8x10‑17] than the most frequently altered HBOC genes BRCA1 (OR, 3.9; 95% CI, 1.6‑9.5; P=0.001), BRCA2 (OR, 7.4; 95% CI, 1.9‑28.9; P=0.002) and CHEK2 (OR, 3.2; 95% CI, 1.0‑9.9; P=0.04). Furthermore, >6% of patients with EC not fulfilling LS or HBOC GGT indication criteria carried a PV in a clinically relevant gene. Carriers of PV in LS genes had a significantly lower age of EC onset than non‑carriers (P=0.01). Another 11.0% of patients carried PV in a candidate gene (the most frequent were FANCA and MUTYH); however, their individual frequencies did not differ from PMCs (except for aggregated frequency of loss‑of‑function variants in POLE/POLD1; OR, 10.44; 95% CI, 1.1‑100.5; P=0.012). The present study demonstrated the importance of GGT in patients with EC. The increased risk of EC of PV carriers in HBOC genes suggests that the diagnosis of EC should be included in the HBOC GGT criteria.
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Copy and paste a formatted citation
Spandidos Publications style
Kral J, Jelinkova S, Zemankova P, Vocka M, Borecka M, Cerna L, Cerna M, Dostalek L, Duskova P, Foretova L, Foretova L, et al: Germline multigene panel testing of patients with endometrial cancer. Oncol Lett 25: 216, 2023.
APA
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L. ... Janatova, M. (2023). Germline multigene panel testing of patients with endometrial cancer. Oncology Letters, 25, 216. https://doi.org/10.3892/ol.2023.13802
MLA
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L., Cerna, M., Dostalek, L., Duskova, P., Foretova, L., Havranek, O., Horackova, K., Hovhannisyan, M., Chvojka, S., Kalousova, M., Kosarova, M., Koudova, M., Krutilkova, V., Machackova, E., Nehasil, P., Novotny, J., Otahalova, B., Puchmajerova, A., Safarikova, M., Slama, J., Stranecky, V., Subrt, I., Tavandzis, S., Zikan, M., Zima, T., Soukupova, J., Kleiblova, P., Kleibl, Z., Janatova, M."Germline multigene panel testing of patients with endometrial cancer". Oncology Letters 25.6 (2023): 216.
Chicago
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L., Cerna, M., Dostalek, L., Duskova, P., Foretova, L., Havranek, O., Horackova, K., Hovhannisyan, M., Chvojka, S., Kalousova, M., Kosarova, M., Koudova, M., Krutilkova, V., Machackova, E., Nehasil, P., Novotny, J., Otahalova, B., Puchmajerova, A., Safarikova, M., Slama, J., Stranecky, V., Subrt, I., Tavandzis, S., Zikan, M., Zima, T., Soukupova, J., Kleiblova, P., Kleibl, Z., Janatova, M."Germline multigene panel testing of patients with endometrial cancer". Oncology Letters 25, no. 6 (2023): 216. https://doi.org/10.3892/ol.2023.13802
Copy and paste a formatted citation
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Spandidos Publications style
Kral J, Jelinkova S, Zemankova P, Vocka M, Borecka M, Cerna L, Cerna M, Dostalek L, Duskova P, Foretova L, Foretova L, et al: Germline multigene panel testing of patients with endometrial cancer. Oncol Lett 25: 216, 2023.
APA
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L. ... Janatova, M. (2023). Germline multigene panel testing of patients with endometrial cancer. Oncology Letters, 25, 216. https://doi.org/10.3892/ol.2023.13802
MLA
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L., Cerna, M., Dostalek, L., Duskova, P., Foretova, L., Havranek, O., Horackova, K., Hovhannisyan, M., Chvojka, S., Kalousova, M., Kosarova, M., Koudova, M., Krutilkova, V., Machackova, E., Nehasil, P., Novotny, J., Otahalova, B., Puchmajerova, A., Safarikova, M., Slama, J., Stranecky, V., Subrt, I., Tavandzis, S., Zikan, M., Zima, T., Soukupova, J., Kleiblova, P., Kleibl, Z., Janatova, M."Germline multigene panel testing of patients with endometrial cancer". Oncology Letters 25.6 (2023): 216.
Chicago
Kral, J., Jelinkova, S., Zemankova, P., Vocka, M., Borecka, M., Cerna, L., Cerna, M., Dostalek, L., Duskova, P., Foretova, L., Havranek, O., Horackova, K., Hovhannisyan, M., Chvojka, S., Kalousova, M., Kosarova, M., Koudova, M., Krutilkova, V., Machackova, E., Nehasil, P., Novotny, J., Otahalova, B., Puchmajerova, A., Safarikova, M., Slama, J., Stranecky, V., Subrt, I., Tavandzis, S., Zikan, M., Zima, T., Soukupova, J., Kleiblova, P., Kleibl, Z., Janatova, M."Germline multigene panel testing of patients with endometrial cancer". Oncology Letters 25, no. 6 (2023): 216. https://doi.org/10.3892/ol.2023.13802
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