Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases-Reference-Cited by-同舟云学术

Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases

Published:2023-06-23 Issue:13 Volume:15 Page:3313
ISSN:2072-6694
Container-title:Cancers
language:en
Short-container-title:Cancers

Author:

Figlioli Gisella¹^ORCID,Billaud Amandine¹,Wang Qin²,Bolla Manjeet K.²,Dennis Joe²^ORCID,Lush Michael²,Kvist Anders³^ORCID,Adank Muriel A.⁴,Ahearn Thomas U.⁵,Antonenkova Natalia N.⁶,Auvinen Päivi⁷⁸⁹,Behrens Sabine¹⁰^ORCID,Bermisheva Marina¹¹,Bogdanova Natalia V.⁶¹²¹³^ORCID,Bojesen Stig E.¹⁴¹⁵¹⁶,Bonanni Bernardo¹⁷^ORCID,Brüning Thomas¹⁸,Camp Nicola J.¹⁹^ORCID,Campbell Archie²⁰²¹^ORCID,Castelao Jose E.²²,Cessna Melissa H.²³,Czene Kamila²⁴,Devilee Peter²⁵²⁶^ORCID,Dörk Thilo¹³^ORCID,Eriksson Mikael²⁴^ORCID,Fasching Peter A.²⁷^ORCID,Flyger Henrik²⁸,Gabrielson Marike²⁴,Gago-Dominguez Manuela²⁹,García-Closas Montserrat⁵,Glendon Gord³⁰³¹,Gómez Garcia Encarna B.³²,González-Neira Anna³³^ORCID,Grassmann Felix²⁴³⁴,Guénel Pascal³⁵,Hahnen Eric³⁶³⁷,Hamann Ute³⁸^ORCID,Hillemanns Peter¹³^ORCID,Hooning Maartje J.³⁹,Hoppe Reiner⁴⁰⁴¹,Howell Anthony⁴²,Humphreys Keith²⁴^ORCID,Jakubowska Anna⁴³⁴⁴^ORCID,Khusnutdinova Elza K.¹¹⁴⁵,Kristensen Vessela N.⁴⁶⁴⁷,Lindblom Annika⁴⁸⁴⁹,Loizidou Maria A.⁵⁰^ORCID,Lubiński Jan⁴³,Mannermaa Arto⁷⁵¹⁵²,Maurer Tabea⁵³,Mavroudis Dimitrios⁵⁴,Newman William G.⁵⁵⁵⁶^ORCID,Obi Nadia⁵⁷^ORCID,Panayiotidis Mihalis I.⁵⁰^ORCID,Radice Paolo⁵⁸^ORCID,Rashid Muhammad U.³⁸⁵⁹^ORCID,Rhenius Valerie⁶⁰,Ruebner Matthias²⁷,Saloustros Emmanouil⁶¹^ORCID,Sawyer Elinor J.⁶²,Schmidt Marjanka K.⁶³⁶⁴⁶⁵^ORCID,Schmutzler Rita K.³⁶³⁷⁶⁶,Shah Mitul⁶⁰,Southey Melissa C.⁶⁷⁶⁸⁶⁹,Tomlinson Ian⁷⁰,Truong Thérèse³⁵,van Veen Elke M.⁵⁵⁵⁶^ORCID,Wendt Camilla⁷¹,Yang Xiaohong R.⁵,Michailidou Kyriaki²⁷²^ORCID,Dunning Alison M.⁶⁰,Pharoah Paul D. P.²⁶⁰⁷³^ORCID,Easton Douglas F.²⁶⁰,Andrulis Irene L.³⁰⁷⁴^ORCID,Evans D. Gareth⁵⁵⁵⁶^ORCID,Hollestelle Antoinette³⁹^ORCID,Chang-Claude Jenny¹⁰⁵³^ORCID,Milne Roger L.⁶⁷⁶⁹⁷⁵,Peterlongo Paolo¹^ORCID, ,

Affiliation:

1. Genome Diagnostics Program, IFOM ETS—The AIRC Institute of Molecular Oncology, 20139 Milan, Italy

2. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK

3. Division of Oncology, Department of Clinical Sciences Lund, Lund University, 22185 Lund, Sweden

4. The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, Family Cancer Clinic, 1066 CX Amsterdam, The Netherlands

5. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services, Bethesda, MD 20892, USA

6. N.N. Alexandrov Research Institute of Oncology and Medical Radiology, 223040 Minsk, Belarus

7. Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland

8. Institute of Clinical Medicine, Oncology, University of Eastern Finland, 70210 Kuopio, Finland

9. Department of Oncology, Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland

10. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

11. Institute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences, 450054 Ufa, Russia

12. Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany

13. Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany

14. Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, 2730 Herlev, Denmark

15. Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, 2730 Herlev, Denmark

16. Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark

17. Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy

18. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), 44789 Bochum, Germany

19. Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA

20. Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK

21. Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH16 4UX, UK

22. Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, 36312 Vigo, Spain

23. Intermountain Health, Salt Lake City, UT 84111, USA

24. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 76 Stockholm, Sweden

25. Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

26. Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

27. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany

28. Department of Breast Surgery, Copenhagen University Hospital, Herlev and Gentofte Hospital, 2730 Herlev, Denmark

29. Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS) Foundation, IDIS Cancer Genetics and Epidemiology Group, Genomic Medicine Group, Complejo Hospitalario Universitario de Santiago, SERGAS, 15706 Santiago de Compostela, Spain

30. Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON M5G 1X5, Canada

31. Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada

32. Department of Clinical Genetics, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands

33. Human Genotyping Unit-CeGen, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain

34. Department of Medicine, Institute for Clinical Research and Systems Medicine, Health and Medical University, 14467 Potsdam, Germany

35. CESP U1018, Inserm “Exposome, Heredity, Cancer and Health” Team, UVSQ, University Paris-Saclay, Gustave Roussy, 94805 Villejuif, France

36. Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany

37. Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany

38. German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, 69120 Heidelberg, Germany

39. Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands

40. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany

41. University of Tübingen, 72074 Tübingen, Germany

42. Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK

43. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland

44. Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland

45. Department of Genetics and Fundamental Medicine, Ufa University of Science and Technology, 450076 Ufa, Russia

46. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0450 Oslo, Norway

47. Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0379 Oslo, Norway

48. Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden

49. Department of Clinical Genetics, Karolinska University Hospital, 171 76 Stockholm, Sweden

50. Department of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, 2371 Nicosia, Cyprus

51. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland

52. Kuopio University Hospital, Biobank of Eastern Finland, 70210 Kuopio, Finland

53. Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany

54. Department of Medical Oncology, University Hospital of Heraklion, 711 10 Heraklion, Greece

55. Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK

56. Manchester Centre for Genomic Medicine, St. Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK

57. University Medical Center Hamburg-Eppendorf, Institute for Medical Biometry and Epidemiology, 20246 Hamburg, Germany

58. Unit of ‘Predictive Medicine: Molecular Bases of Genetic Risk’, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy

59. Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore 54000, Pakistan

60. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK

61. Department of Oncology, University Hospital of Larissa, 411 10 Larissa, Greece

62. King’s College London, School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy’s Campus, London SE1 9RT, UK

63. Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands

64. Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands

65. Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

66. Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany

67. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia

68. Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC 3000, Australia

69. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia

70. Cancer Research Centre, The University of Edinburgh, Edinburgh EH4 2XU, UK

71. Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, 118 83 Stockholm, Sweden

72. Biostatistics Unit, The Cyprus Institute of Neurology & Genetics, 2371 Nicosia, Cyprus

73. Department of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, CA 90069, USA

74. Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada

75. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia

Abstract

FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Link

https://www.mdpi.com/2072-6694/15/13/3313/pdf

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