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; Bruning, T; Camp, NJ; Campbell, A; Castelao, JE; Cessna, MH; NBCS Collaborators; Czene, K; Devilee, P; Dork, T; Eriksson, M; Fasching, PA; Flyger, H; Gabrielson, M; Gago-Dominguez, M; Garcia-Closas, M; Glendon, G; Gomez Garcia, EB; Gonzalez-Neira, A; Grassmann, F; Guenel, 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; Lubinski, 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

Author(s): 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; Bruning, T; Camp, NJ; Campbell, A; Castelao, JE; Cessna, MH; NBCS Collaborators; Czene, K; Devilee, P; Dork, T; Eriksson, M; Fasching, PA; Flyger, H; Gabrielson, M; Gago-Dominguez, M; Garcia-Closas, M; Glendon, G; Gomez Garcia, EB; Gonzalez-Neira, A; Grassmann, F; Guenel, 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; Lubinski, 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;
Details: Publication Year 2023-06-23,Volume 15,Issue #13,Page 3313
Journal Title: Cancers
Publication Type: Research article
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.
Publisher: MDPI
Keywords: FANCM PTVs spectrum; PTVs; breast cancer predisposition; breast cancer risk factors; protein truncating variants
Department(s): Laboratory Research
PubMed ID: 37444426
Publisher's Version: https://doi.org/10.3390/cancers15133313
Open Access at Publisher's Site: https://doi.org/10.3390/cancers15133313
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-09-14 03:09:12

Last Modified: 2023-09-14 03:09:44