The spectrum of fancm 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 CortesiEsther Darder, Jesús Del Valle, Orland Diez, Séverine Eon-Marchais, Florentia Fostira, 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, 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, ENIGMA Consortium

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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.

Original languageEnglish
Article number292
Number of pages10
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Breast cancer predisposition
  • Breast cancer risk factors
  • FANCM truncating variants
  • Mutation spectrum
  • PTVs

Cite this

Figlioli, G., Kvist, A., Tham, E., Soukupova, J., Kleiblova, P., Muranen, T. A., Andrieu, N., Azzollini, J., Balmaña, J., Barroso, A., Benítez, J., Bertelsen, B., Blanco, A., Bonanni, B., Borg, Å., Brunet, J., Calistri, D., Calvello, M., Chvojka, S., ... ENIGMA Consortium (2020). The spectrum of fancm protein truncating variants in European breast cancer cases. Cancers, 12(2), [292]. https://doi.org/10.3390/cancers12020292