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

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, Cessna MH, Czene K, Devilee P, Dörk T, Eriksson M, Fasching P, 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, 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, Rübner 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 PD, Easton DF, Andrulis IL, Evans DG, Hollestelle A, Chang-Claude J, Milne RL, Peterlongo P (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 15

Article Number: 3313

Journal Issue: 13

DOI: 10.3390/cancers15133313

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.

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

Karolinska Institute Sweden (SE) Universitätsklinikum Köln Germany (DE) University of Cambridge United Kingdom (GB) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Lund University / Lunds universitet Sweden (SE) Antoni van Leeuwenhoek Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) University of Eastern Finland Finland (FI) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Copenhagen University Hospital Denmark (DK) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) Germany (DE) University of Utah United States (USA) (US) University of Edinburgh United Kingdom (GB) Instituto de Investigación Sanitaria Galicia Sur Spain (ES) Intermountain Healthcare United States (USA) (US) Leiden University Medical Center Netherlands (NL) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) Mount Sinai Hospital (MSH) Canada (CA) Maastricht University Netherlands (NL) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) Erasmus University Medical Center (MC) Netherlands (NL) Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie Germany (DE) University of Manchester United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Cyprus Institute of Neurology and Genetics Cyprus (CY) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University General Hospital of Heraklion Greece (GR) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) General University Hospital of Larissa Greece (GR) King’s College London United Kingdom (GB) Netherlands Cancer Institute (NKI) Netherlands (NL) Monash University Australia (AU)

How to cite

APA:

Figlioli, G., Billaud, A., Wang, Q., Bolla, M.K., Dennis, J., Lush, M.,... Peterlongo, P. (2023). Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases. Cancers, 15(13). https://doi.org/10.3390/cancers15133313

MLA:

Figlioli, Gisella, et al. "Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases." Cancers 15.13 (2023).

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