Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases.
About this Publication
Title
Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases.
Pubmed ID
37444426
(View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancers (Basel). 2023 Jun 23; Volume 15 (Issue 13)
Authors
Figlioli G, Billaud A, Wang Q, Bolla MK, Dennis J, Lush M, Kvist A, Adank MA, Ahearn TU, Antonenkova NN, Auvinen P, Behrens S, Bermisheva M, Bogdanova NV, Bojesen SE, Bonanni B, Brüning T, Camp NJ, Campbell A, Castelao JE, ...show more Cessna MH, Nbcs Collaborators, Czene K, Devilee P, Dörk T, Eriksson M, Fasching PA, Flyger H, Gabrielson M, Gago-Dominguez M, García-Closas M, Glendon G, Gómez Garcia EB, González-Neira A, Grassmann F, Guénel P, Hahnen E, Hamann U, Hillemanns P, Hooning MJ, Hoppe R, Howell A, Humphreys K, kConFab Investigators, Jakubowska A, Khusnutdinova EK, Kristensen VN, Lindblom A, Loizidou MA, Lubiński J, Mannermaa A, Maurer T, Mavroudis D, Newman WG, Obi N, Panayiotidis MI, Radice P, Rashid MU, Rhenius V, Ruebner M, Saloustros E, Sawyer EJ, Schmidt MK, Schmutzler RK, Shah M, Southey MC, Tomlinson I, Truong T, van Veen EM, Wendt C, Yang XR, Michailidou K, Dunning AM, Pharoah PDP, Easton DF, Andrulis IL, Evans DG, Hollestelle A, Chang-Claude J, Milne RL, Peterlongo P
Affiliations
- Genome Diagnostics Program, IFOM ETS-The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
- Division of Oncology, Department of Clinical Sciences Lund, Lund University, 22185 Lund, Sweden.
- The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Family Cancer Clinic, 1066 CX Amsterdam, The Netherlands.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services, Bethesda, MD 20892, USA.
- N.N. Alexandrov Research Institute of Oncology and Medical Radiology, 223040 Minsk, Belarus.
- Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
- Institute of Biochemistry and Genetics of the Ufa Federal Research Centre of the Russian Academy of Sciences, 450054 Ufa, Russia.
- Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, 2730 Herlev, Denmark.
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy.
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), 44789 Bochum, Germany.
- Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
- Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, 36312 Vigo, Spain.
- Intermountain Health, Salt Lake City, UT 84111, USA.
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, 0379 Oslo, Norway.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 76 Stockholm, Sweden.
- Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
- Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany.
- Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
- Department of Breast Surgery, Copenhagen University Hospital, Herlev and Gentofte Hospital, 2730 Herlev, Denmark.
- 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.
- Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON M5G 1X5, Canada.
- Department of Clinical Genetics, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
- Human Genotyping Unit-CeGen, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
- CESP U1018, Inserm "Exposome, Heredity, Cancer and Health" Team, UVSQ, University Paris-Saclay, Gustave Roussy, 94805 Villejuif, France.
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
- German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, 69120 Heidelberg, Germany.
- Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK.
- Research Department, Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia.
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland.
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0450 Oslo, Norway.
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.
- Department of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, 2371 Nicosia, Cyprus.
- Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
- Department of Medical Oncology, University Hospital of Heraklion, 711 10 Heraklion, Greece.
- Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK.
- University Medical Center Hamburg-Eppendorf, Institute for Medical Biometry and Epidemiology, 20246 Hamburg, Germany.
- Unit of 'Predictive Medicine: Molecular Bases of Genetic Risk', Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy.
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
- Department of Oncology, University Hospital of Larissa, 411 10 Larissa, Greece.
- King's College London, School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, London SE1 9RT, UK.
- Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia.
- Cancer Research Centre, The University of Edinburgh, Edinburgh EH4 2XU, UK.
- Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, 118 83 Stockholm, Sweden.
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.
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