Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases
(2023) In Cancers 15(13).- 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... (More)
- 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. © 2023 by the authors. (Less)
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https://lup.lub.lu.se/record/e6ae4001-9360-46fc-96ad-56092b67a108
- author
- Figlioli, G. ; Kvist, A. LU and Peterlongo, P.
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- breast cancer predisposition, breast cancer risk factors, FANCM PTVs spectrum, protein truncating variants, PTVs, Article, Australia, breast cancer, Canada, cancer risk, cancer susceptibility, cohort analysis, Eastern Europe, European, FANCM gene, female, gene, gene frequency, genetic variability, heterozygote, human, Lithuania, major clinical study, prevalence, risk factor, United States
- in
- Cancers
- volume
- 15
- issue
- 13
- article number
- 3313
- publisher
- MDPI AG
- external identifiers
-
- scopus:85165009430
- ISSN
- 2072-6694
- DOI
- 10.3390/cancers15133313
- language
- English
- LU publication?
- yes
- id
- e6ae4001-9360-46fc-96ad-56092b67a108
- date added to LUP
- 2023-11-20 11:27:09
- date last changed
- 2023-11-20 11:29:18
@article{e6ae4001-9360-46fc-96ad-56092b67a108, 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. © 2023 by the authors.}}, author = {{Figlioli, G. and Kvist, A. and Peterlongo, P.}}, issn = {{2072-6694}}, keywords = {{breast cancer predisposition; breast cancer risk factors; FANCM PTVs spectrum; protein truncating variants; PTVs; Article; Australia; breast cancer; Canada; cancer risk; cancer susceptibility; cohort analysis; Eastern Europe; European; FANCM gene; female; gene; gene frequency; genetic variability; heterozygote; human; Lithuania; major clinical study; prevalence; risk factor; United States}}, language = {{eng}}, number = {{13}}, publisher = {{MDPI AG}}, series = {{Cancers}}, title = {{Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases}}, url = {{http://dx.doi.org/10.3390/cancers15133313}}, doi = {{10.3390/cancers15133313}}, volume = {{15}}, year = {{2023}}, }