The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Figlioli, Gisella; Kvist, Anders; Tham, Emma; Soukupova, Jana; Kleiblova, Petra; Muranen, Taru A; Andrieu, Nadine; Azzollini, Jacopo; Balmaña, Judith; Barroso, Alicia; Benítez, Javier; Bertelsen, Birgitte; Blanco, Ana; Bonanni, Bernardo; Borg, Åke; Brunet, Joan; Calistri, Daniele; Calvello, Mariarosaria; Chvojka, Stepan; Cortesi, Laura

doi:10.3390/cancers12020292

The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Journal

Cancers

Date Issued

2020

Author(s)

Figlioli, Gisella

Kvist, Anders

Tham, Emma

Soukupova, Jana

Kleiblova, Petra

Muranen, Taru A

Andrieu, Nadine

Azzollini, Jacopo

Balmaña, Judith

Barroso, Alicia

Benítez, Javier

Bertelsen, Birgitte

Blanco, Ana

Bonanni, Bernardo

Borg, Åke

Brunet, Joan

Calistri, Daniele

Calvello, Mariarosaria

Chvojka, Stepan

Cortesi, Laura

Darder, Esther

Del Valle, Jesús

Diez, Orland

Eon-Marchais, Séverine

Fostira, Florentia

Gensini, Francesca

Houdayer, Claude

Janatova, Marketa

Kiiski, Johanna I

Konstantopoulou, Irene

Kubelka-Sabit, Katerina

Lázaro, Conxi

Lesueur, Fabienne

Manoukian, Siranoush

Marcinkute, Ruta

Mickys, Ugnius

Moncoutier, Virginie

Myszka, Aleksander

Nguyen-Dumont, Tu

Nielsen, Finn Cilius

Norvilas, Rimvydas

Olah, Edith

Osorio, Ana

Papi, Laura

Peissel, Bernard

Peixoto, Ana

Plaseska-Karanfilska, Dijana

Pócza, Timea

Rossing, Maria

Rudaitis, Vilius

Santamariña, Marta

Santos, Catarina

Southey, Melissa C

Stoppa-Lyonnet, Dominique

Teixeira, Manuel

Törngren, Therese

Toss, Angela

Urioste, Miguel

Vega, Ana

Vlckova, Zdenka

Yannoukakos, Drakoulis

Zampiga, Valentina

Kleibl, Zdenek

Radice, Paolo

Nevanlinna, Heli

Ehrencrona, Hans

Janavicius, Ramunas

Peterlongo, Paolo

DOI

10.3390/cancers12020292

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.