Cancers (Jan 2020)
The Spectrum of <i>FANCM</i> Protein Truncating Variants in European Breast Cancer Cases
- Gisella Figlioli,
- Anders Kvist,
- Emma Tham,
- Jana Soukupova,
- Petra Kleiblova,
- Taru A Muranen,
- Nadine Andrieu,
- Jacopo Azzollini,
- Judith Balmaña,
- Alicia Barroso,
- Javier Benítez,
- Birgitte Bertelsen,
- Ana Blanco,
- Bernardo Bonanni,
- Åke Borg,
- Joan Brunet,
- Daniele Calistri,
- Mariarosaria Calvello,
- Stepan Chvojka,
- Laura Cortesi,
- Esther Darder,
- Jesús Del Valle,
- Orland Diez,
- ENIGMA Consortium,
- Séverine Eon-Marchais,
- Florentia Fostira,
- GENESIS Study Collaborators,
- Francesca Gensini,
- Claude Houdayer,
- Marketa Janatova,
- Johanna I Kiiski,
- Irene Konstantopoulou,
- Katerina Kubelka-Sabit,
- Conxi Lázaro,
- Fabienne Lesueur,
- Siranoush Manoukian,
- Ruta Marcinkute,
- Ugnius Mickys,
- Virginie Moncoutier,
- SWE-BRCA Group,
- Aleksander Myszka,
- Tu Nguyen-Dumont,
- Finn Cilius Nielsen,
- Rimvydas Norvilas,
- Edith Olah,
- Ana Osorio,
- Laura Papi,
- Bernard Peissel,
- Ana Peixoto,
- Dijana Plaseska-Karanfilska,
- Timea Pócza,
- Maria Rossing,
- Vilius Rudaitis,
- Marta Santamariña,
- Catarina Santos,
- Snezhana Smichkoska,
- Melissa C Southey,
- Dominique Stoppa-Lyonnet,
- Manuel Teixeira,
- Therese Törngren,
- Angela Toss,
- Miguel Urioste,
- Ana Vega,
- Zdenka Vlckova,
- Drakoulis Yannoukakos,
- Valentina Zampiga,
- Zdenek Kleibl,
- Paolo Radice,
- Heli Nevanlinna,
- Hans Ehrencrona,
- Ramunas Janavicius,
- Paolo Peterlongo
Affiliations
- Gisella Figlioli
- Genome Diagnostics Program, IFOM - the FIRC Institute for Molecular Oncology, Milan 20139, Italy
- Anders Kvist
- Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE-22381, Sweden
- Emma Tham
- Department of Clinical Genetics, Karolinska University Hospital and Department of Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden
- Jana Soukupova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 12853, Czech Republic
- Petra Kleiblova
- Institute of Biology and Medical Genetics, General University Hospital and First Faculty of Medicine, Charles University, Prague 12800, Czech Republic
- Taru A Muranen
- Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, HUS, Helsinki 00029, Finland
- Nadine Andrieu
- Inserm, U900, Institut Curie, PSL University, Paris F-75005, France
- Jacopo Azzollini
- Department of Medical Oncology and Hematology, Unit of Medical Genetics Fondazione, IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Judith Balmaña
- Hereditary Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona 08035, Spain
- Alicia Barroso
- Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain
- Javier Benítez
- Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain
- Birgitte Bertelsen
- Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
- Ana Blanco
- Fundación Pública Galega Medicina Xenómica-SERGAS, Santiago de Compostela 15706, Spain
- Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan 20141, Italy
- Åke Borg
- Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE-22381, Sweden
- Joan Brunet
- Hereditary Cancer Program, Catalan Institute of Oncology, ONCOBELL-IDIBELL-IDIBGI-IGTP, CIBERONC, Barcelona 08908, Spain
- Daniele Calistri
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
- Mariarosaria Calvello
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan 20141, Italy
- Stepan Chvojka
- Centre for Medical Genetics and Reproductive Medicine, Gennet, Prague 17000, Czech Republic
- Laura Cortesi
- University Modena Hospital, Modena 41124, Italy
- Esther Darder
- Hereditary Cancer Program, Catalan Institute of Oncology, ONCOBELL-IDIBELL-IDIBGI-IGTP, CIBERONC, Barcelona 08908, Spain
- Jesús Del Valle
- Hereditary Cancer Program, Catalan Institute of Oncology, ONCOBELL-IDIBELL-IDIBGI-IGTP, CIBERONC, Barcelona 08908, Spain
- Orland Diez
- Hereditary Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona 08035, Spain
- ENIGMA Consortium
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Séverine Eon-Marchais
- Inserm, U900, Institut Curie, PSL University, Paris F-75005, France
- Florentia Fostira
- InRASTES, Molecular Diagnostics Laboratory, National Centre for Scientific Research “Demokritos”, Athens 15310, Greece
- GENESIS Study Collaborators
- Inserm, U900, Institut Curie, PSL University, Paris F-75005, France
- Francesca Gensini
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence 50134, Italy
- Claude Houdayer
- Genetics Department, F76000 and Normandy University, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
- Marketa Janatova
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 12853, Czech Republic
- Johanna I Kiiski
- Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, HUS, Helsinki 00029, Finland
- Irene Konstantopoulou
- InRASTES, Molecular Diagnostics Laboratory, National Centre for Scientific Research “Demokritos”, Athens 15310, Greece
- Katerina Kubelka-Sabit
- Department of Histopathology and Cytology, Clinical Hospital Acibadem Sistina, Skopje 1000, Republic of North Macedonia
- Conxi Lázaro
- Hereditary Cancer Program, Catalan Institute of Oncology, ONCOBELL-IDIBELL-IDIBGI-IGTP, CIBERONC, Barcelona 08908, Spain
- Fabienne Lesueur
- Inserm, U900, Institut Curie, PSL University, Paris F-75005, France
- Siranoush Manoukian
- Department of Medical Oncology and Hematology, Unit of Medical Genetics Fondazione, IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Ruta Marcinkute
- Hereditary Cancer Center, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius 08410, Lithuania
- Ugnius Mickys
- National Center of Pathology, Vilnius University Hospital Santaros Klinikos, Vilnius 08410, Lithuania
- Virginie Moncoutier
- Service de Génétique, Institut Curie, Inserm, U830, Paris Descartes University, Paris F-75005, France
- SWE-BRCA Group
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund SE-22100, Sweden
- Aleksander Myszka
- Institute of Medical Sciences, University of Rzeszow, Rzeszow 35-310, Poland
- Tu Nguyen-Dumont
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton 3168, Australia
- Finn Cilius Nielsen
- Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
- Rimvydas Norvilas
- Hereditary Cancer Center, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius 08410, Lithuania
- Edith Olah
- Department of Molecular Genetics, National Institute of Oncology, Budapest 1122, Hungary
- Ana Osorio
- Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain
- Laura Papi
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence 50134, Italy
- Bernard Peissel
- Department of Medical Oncology and Hematology, Unit of Medical Genetics Fondazione, IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Ana Peixoto
- Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto 4200-072, Portugal
- Dijana Plaseska-Karanfilska
- Research Centre for Genetic Engineering and Biotechnology ‘Georgi D. Efremov’, Macedonian Academy of Sciences and Arts, Skopje 1000, Republic of North Macedonia
- Timea Pócza
- Department of Molecular Genetics, National Institute of Oncology, Budapest 1122, Hungary
- Maria Rossing
- Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
- Vilius Rudaitis
- Department of Gynaecology, Center of Obsterics and Gynaecology, Vilnius University Hospital Santaros Klinikos, Vilnius 08410, Lithuania
- Marta Santamariña
- Fundación Pública Galega Medicina Xenómica-SERGAS, Santiago de Compostela 15706, Spain
- Catarina Santos
- Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto 4200-072, Portugal
- Snezhana Smichkoska
- Medical Faculty, University Clinic of Radiotherapy and Oncology, Ss. Cyril and Methodius University in Skopje, Skopje 1000, Republic of North Macedonia
- Melissa C Southey
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton 3168, Australia
- Dominique Stoppa-Lyonnet
- Service de Génétique, Institut Curie, Inserm, U830, Paris Descartes University, Paris F-75005, France
- Manuel Teixeira
- Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto 4200-072, Portugal
- Therese Törngren
- Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE-22381, Sweden
- Angela Toss
- University Modena Hospital, Modena 41124, Italy
- Miguel Urioste
- Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid 28029, Spain
- Ana Vega
- Fundación Pública Galega Medicina Xenómica-SERGAS, Santiago de Compostela 15706, Spain
- Zdenka Vlckova
- Department of Medical Genetics, GHC Genetics, Prague 11000, Czech Republic
- Drakoulis Yannoukakos
- InRASTES, Molecular Diagnostics Laboratory, National Centre for Scientific Research “Demokritos”, Athens 15310, Greece
- Valentina Zampiga
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
- Zdenek Kleibl
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 12853, Czech Republic
- Paolo Radice
- Department of Research, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, HUS, Helsinki 00029, Finland
- Hans Ehrencrona
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund SE-22100, Sweden
- Ramunas Janavicius
- Hereditary Cancer Center, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius 08410, Lithuania
- Paolo Peterlongo
- Genome Diagnostics Program, IFOM - the FIRC Institute for Molecular Oncology, Milan 20139, Italy
- DOI
- https://doi.org/10.3390/cancers12020292
- Journal volume & issue
-
Vol. 12,
no. 2
p. 292
Abstract
Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2−4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.
Keywords
- breast cancer predisposition
- breast cancer risk factors
- <i>fancm</i> truncating variants
- mutation spectrum
- ptvs
