Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases
| Title: | Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases |
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| Authors: | Gisella Figlioli; Amandine Billaud; Qin Wang; Manjeet K. Bolla; Joe Dennis; Michael Lush; Anders Kvist; Muriel A. Adank; Thomas U. Ahearn; Natalia N. Antonenkova; Päivi Auvinen; Sabine Behrens; Marina Bermisheva; Natalia V. Bogdanova; Stig E. Bojesen; Bernardo Bonanni; Thomas Brüning; Nicola J. Camp; Archie Campbell; Jose E. Castelao; Melissa H. Cessna; NBCS Collaborators; Kamila Czene; Peter Devilee; Thilo Dörk; Mikael Eriksson; Peter A. Fasching; Henrik Flyger; Marike Gabrielson; Manuela Gago-Dominguez; Montserrat García-Closas; Gord Glendon; Encarna B. Gómez Garcia; Anna González-Neira; Felix Grassmann; Pascal Guénel; Eric Hahnen; Ute Hamann; Peter Hillemanns; Maartje J. Hooning; Reiner Hoppe; Anthony Howell; Keith Humphreys; kConFab Investigators; Anna Jakubowska; Elza K. Khusnutdinova; Vessela N. Kristensen; Annika Lindblom; Maria A. Loizidou; Jan Lubiński; Arto Mannermaa; Tabea Maurer; Dimitrios Mavroudis; William G. Newman; Nadia Obi; Mihalis I. Panayiotidis; Paolo Radice; Muhammad U. Rashid; Valerie Rhenius; Matthias Ruebner; Emmanouil Saloustros; Elinor J. Sawyer; Marjanka K. Schmidt; Rita K. Schmutzler; Mitul Shah; Melissa C. Southey; Ian Tomlinson; Thérèse Truong; Elke M. van Veen; Camilla Wendt; Xiaohong R. Yang; Kyriaki Michailidou; Alison M. Dunning; Paul D. P. Pharoah; Douglas F. Easton; Irene L. Andrulis; D. Gareth Evans; Antoinette Hollestelle; Jenny Chang-Claude; Roger L. Milne; Paolo Peterlongo |
| Source: | Cancers, Vol 15, Iss 13, p 3313 (2023) |
| Publisher Information: | MDPI AG |
| Publication Year: | 2023 |
| Collection: | Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: | breast cancer predisposition; breast cancer risk factors; FANCM PTVs spectrum; protein truncating variants; PTVs; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282 |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | https://www.mdpi.com/2072-6694/15/13/3313; https://doaj.org/toc/2072-6694; https://doaj.org/article/01386115a4d4453ab801980b7cc4e9be |
| DOI: | 10.3390/cancers15133313 |
| Availability: | https://doi.org/10.3390/cancers15133313; https://doaj.org/article/01386115a4d4453ab801980b7cc4e9be |
| Accession Number: | edsbas.930BD20B |
| Database: | BASE |