Abstract
| Original language | English |
|---|---|
| Journal | Cancers |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2020 |
Keywords
- Breast cancer predisposition
- Breast cancer risk factors
- FANCM truncating variants
- Mutation spectrum
- PTVs
- adult
- aged
- Article
- controlled study
- Czech Republic
- Denmark
- estrogen receptor negative breast cancer
- estrogen receptor positive breast cancer
- FANCM gene
- female
- Finland
- France
- gene
- gene frequency
- gene sequence
- genetic association
- genetic variability
- Greece
- human
- Hungary
- Lithuania
- major clinical study
- middle aged
- Poland
- Portugal
- protein truncating variant
- Spain
- Sweden
- tumor suppressor gene
- very elderly
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The spectrum of fancm protein truncating variants in European breast cancer cases. / 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.; Cortesi, L.; Darder, E.; Del Valle, J.; Diez, O.; Eon-Marchais, S.; Fostira, F.; Gensini, F.; Houdayer, C.; Janatova, M.; Kiiski, J.I.; Konstantopoulou, I.; Kubelka-Sabit, K.; Lázaro, C.; Lesueur, F.; Manoukian, S.; Marcinkute, R.; Mickys, U.; Moncoutier, V.; Myszka, A.; Nguyen-Dumont, T.; Nielsen, F.C.; Norvilas, R.; Olah, E.; Osorio, A.; Papi, L.; Peissel, B.; Peixoto, A.; Plaseska-Karanfilska, D.; Pócza, T.; Rossing, M.; Rudaitis, V.; Santamariña, M.; Santos, C.; Smichkoska, S.; Southey, M.C.; Stoppa-Lyonnet, D.; Teixeira, M.; Törngren, T.; Toss, A.; Urioste, M.; Vega, A.; Vlckova, Z.; Yannoukakos, D.; Zampiga, V.; Kleibl, Z.; Radice, P.; Nevanlinna, H.; Ehrencrona, H.; Janavicius, R.; Peterlongo, P.; Consortium, ENIGMA.
In: Cancers, Vol. 12, No. 2, 2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The spectrum of fancm protein truncating variants in European breast cancer cases
AU - Figlioli, G.
AU - Kvist, A.
AU - Tham, E.
AU - Soukupova, J.
AU - Kleiblova, P.
AU - Muranen, T.A.
AU - Andrieu, N.
AU - Azzollini, J.
AU - Balmaña, J.
AU - Barroso, A.
AU - Benítez, J.
AU - Bertelsen, B.
AU - Blanco, A.
AU - Bonanni, B.
AU - Borg, Å.
AU - Brunet, J.
AU - Calistri, D.
AU - Calvello, M.
AU - Chvojka, S.
AU - Cortesi, L.
AU - Darder, E.
AU - Del Valle, J.
AU - Diez, O.
AU - Eon-Marchais, S.
AU - Fostira, F.
AU - Gensini, F.
AU - Houdayer, C.
AU - Janatova, M.
AU - Kiiski, J.I.
AU - Konstantopoulou, I.
AU - Kubelka-Sabit, K.
AU - Lázaro, C.
AU - Lesueur, F.
AU - Manoukian, S.
AU - Marcinkute, R.
AU - Mickys, U.
AU - Moncoutier, V.
AU - Myszka, A.
AU - Nguyen-Dumont, T.
AU - Nielsen, F.C.
AU - Norvilas, R.
AU - Olah, E.
AU - Osorio, A.
AU - Papi, L.
AU - Peissel, B.
AU - Peixoto, A.
AU - Plaseska-Karanfilska, D.
AU - Pócza, T.
AU - Rossing, M.
AU - Rudaitis, V.
AU - Santamariña, M.
AU - Santos, C.
AU - Smichkoska, S.
AU - Southey, M.C.
AU - Stoppa-Lyonnet, D.
AU - Teixeira, M.
AU - Törngren, T.
AU - Toss, A.
AU - Urioste, M.
AU - Vega, A.
AU - Vlckova, Z.
AU - Yannoukakos, D.
AU - Zampiga, V.
AU - Kleibl, Z.
AU - Radice, P.
AU - Nevanlinna, H.
AU - Ehrencrona, H.
AU - Janavicius, R.
AU - Peterlongo, P.
AU - Consortium, ENIGMA
N1 - Cited By :2 Export Date: 3 March 2021 Correspondence Address: Peterlongo, P.; IFOM-the FIRC Institute for Molecular OncologyItaly; email: paolo.peterlongo@ifom.eu Funding details: APP1029974, APP1074383 Funding details: IN607B Funding details: INCa-DGOS-4654, b2008-029/LL-LC Funding details: K-112228 Funding details: INT15/00070, INT16/00154, INT17/00133 Funding details: P-MIP-20-25, SEN18/2015 Funding details: VR0182 Funding details: Fundación Mutua Madrileña Funding details: Gene Bridges, H2020 Funding details: Rare Diseases Clinical Research Network, RDCRN Funding details: National Health and Medical Research Council, NHMRC Funding details: National Breast Cancer Foundation, NBCF, ECF-17-001 Funding details: Generalitat de Catalunya, 2017SGR1282, 2017SGR496 Funding details: Ministerstvo Zdravotnictvà Ceské Republiky, MZCR, PI16/00440, PI19/00640 Funding details: Hungarian Scientific Research Fund, OTKA, KTIA-OTKA CK-80745 Funding details: Ligue Contre le Cancer Funding details: Instituto de Salud Carlos III, ISCIII Funding details: Fondazione Umberto Veronesi Funding details: State Government of Victoria Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC, 16732, IG2015 Funding details: Syöpäjärjestöt Funding details: European Regional Development Fund, FEDER, PI16/00563, PI19/00553 Funding details: Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, ER17P1AC7112/2018 Funding text 1: Funding: This research was partially funded by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo, a fellowship from Fondazione Umberto Veronesi to G. Figlioli and by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds. E. Tham is supported by Region Stockholm (ALF). The Czech study was supported by a grant of the Ministry of Health of the Czech Republic NV16-29959A. CNIO study was partially supported by projects PI16/00440 and PI19/00640, supported by the Instituto de Salud Carlos III, cofunded by European Regional Development Fund (ERDF), the Spanish Network on Rare Diseases (CIBERER) and BRIDGES project H2020. Financial support for GENESIS resource and genotyping was provided by the Ligue Nationale contre le Cancer (grants PRE05/DSL, PRE07/DSL, PRE11/NA), the French National Institute of Cancer (INCa grant No b2008-029/LL-LC) and the comprehensive cancer center SiRIC, (Site de Recherche Intégrée sur le Cancer: Grant INCa-DGOS-4654). HEBCS was funded by Helsinki University Hospital Research Fund, Sigrid Juselius Foundation, The cancer Society of Finland. A.Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII) through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). This work was supported by the Australian National Health and Medical Research Council (APP1029974 and APP1074383) and by a Victorian Life Sciences Computation Initiative grant (number VR0182) on its Peak Computing Facility, an initiative of the Victorian Government. T.N-D is a Career Development Fellow of the National Breast Cancer Foundation (Australia, ECF-17-001). M.C.S. is a National Health and Medical Research Council (Australia) Senior Research Fellow. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI OTKA K-112228 to E. Olah. Lithuanian study was supported by The Research Council of Lithuania grant SEN18/2015 and P-MIP-20-25 to R. Janavicius. The ICO was supported by the Carlos III National Health Institute funded by FEDER funds—a way to build Europe—[PI16/00563, PI19/00553 and CIBERONC]; the Government of Catalonia [Pla estratègic de recerca i innovació en salut (PERIS) Project MedPerCan, 2017SGR1282 and 2017SGR496]; and CERCA program. Funding text 2: This research was partially funded by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo, a fellowship from Fondazione Umberto Veronesi to G. Figlioli and by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds. E. Tham is supported by Region Stockholm (ALF). The Czech study was supported by a grant of the Ministry of Health of the Czech Republic NV16-29959A. CNIO study was partially supported by projects PI16/00440 and PI19/00640, supported by the Instituto de Salud Carlos III, cofunded by European Regional Development Fund (ERDF), the Spanish Network on Rare Diseases (CIBERER) and BRIDGES project H2020. Financial support for GENESIS resource and genotyping was provided by the Ligue Nationale contre le Cancer (grants PRE05/DSL, PRE07/DSL, PRE11/NA), the French National Institute of Cancer (INCa grant No b2008-029/LL-LC) and the comprehensive cancer center SiRIC, (Site de Recherche Int?gr?e sur le Cancer: Grant INCa-DGOS-4654). HEBCS was funded by Helsinki University Hospital Research Fund, Sigrid Juselius Foundation, The cancer Society of Finland. A.Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII) through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigaci?n Biom?dica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundaci?n Mutua Madrile?a (call 2018). This work was supported by the Australian National Health and Medical Research Council (APP1029974 and APP1074383) and by a Victorian Life Sciences Computation Initiative grant (number VR0182) on its Peak Computing Facility, an initiative of the Victorian Government. T.N-D is a Career Development Fellow of the National Breast Cancer Foundation (Australia, ECF-17-001). M.C.S. is a National Health and Medical Research Council (Australia) Senior Research Fellow. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI OTKA K-112228 to E. Olah. Lithuanian study was supported by The Research Council of Lithuania grant SEN18/2015 and P-MIP-20-25 to R. Janavicius. The ICO was supported by the Carlos III National Health Institute funded by FEDER funds?a way to build Europe?[PI16/00563, PI19/00553 and CIBERONC]; the Government of Catalonia [Pla estrat?gic de recerca i innovaci? en salut (PERIS) Project MedPerCan, 2017SGR1282 and 2017SGR496]; and CERCA program. References: Meetei, A.R., Medhurst, A.L., Ling, C., Xue, Y., Singh, T.R., Bier, P., Steltenpool, J., Mathew, C.G., A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M (2005) Nat. Genet., 37, pp. 958-963; Bogliolo, M., Bluteau, D., Lespinasse, J., Pujol, R., Vasquez, N., D’Enghien, C.D., Stoppa-Lyonnet, D., Surralles, J., Biallelic truncating FANCM mutations cause early-onset cancer but not Fanconi anemia (2018) Genet. Med., 20, pp. 458-463; Catucci, I., Osorio, A., Arver, B., Neidhardt, G., Bogliolo, M., Zanardi, F., Riboni, M., Azzollini, J., Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility (2018) Genet. Med., 20, pp. 452-457; Lek, M., Karczewski, K.J., Minikel, E.V., Samocha, K.E., Banks, E., Fennell, T., O’donnell-Luria, A.H., Cummings, B.B., Analysis of protein-coding genetic variation in 60,706 humans (2016) Nature, 536, pp. 285-291; Kiiski, J.I., Pelttari, L.M., Khan, S., Freysteinsdottir, E.S., Reynisdottir, I., Hart, S.N., Shimelis, H., Schleutker, J., Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer (2014) Proc. Natl. Acad. Sci. USA, 111, pp. 15172-15177; Kiiski, J.I., Fagerholm, R., Tervasmaki, A., Pelttari, L.M., Khan, S., Jamshidi, M., Mantere, T., Bartkova, J., FANCM c.5101C>T mutation associates with breast cancer survival and treatment outcome (2016) Int. J. Cancer, 139, pp. 2760-2770; Peterlongo, P., Catucci, I., Colombo, M., Caleca, L., Mucaki, E., Bogliolo, M., Marin, M., Pensotti, V., FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor (2015) Hum. Mol. Genet., 24, pp. 5345-5355; Kiiski, J.I., Tervasmaki, A., Pelttari, L.M., Khan, S., Mantere, T., Pylkas, K., Mannermaa, A., Borg, A., FANCM mutation c.5791C>T is a risk factor for triple-negative breast cancer in the Finnish population (2017) Breast Cancer Res. Treat., 166, pp. 217-226; Neidhardt, G., Hauke, J., Ramser, J., Gross, E., Gehrig, A., Muller, C.R., Kahlert, A.K., Niederacher, D., Association Between Loss-of-Function Mutations Within the FANCM Gene and Early-Onset Familial Breast Cancer (2017) JAMA Oncol, 3, pp. 1245-1248; Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S.V., Pujol, R., Kiiski, J.I., Dennis, J., The FANCM:P.Arg658* truncating variant is associated with risk of triple-negative breast cancer (2019) Npj Breast Cancer, p. 5; Shimelis, H., Laduca, H., Hu, C., Hart, S.N., Na, J., Thomas, A., Akinhanmi, M., Cox, A., Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing (2018) J. Natl. Cancer Inst., 110, pp. 855-862; Spurdle, A.B., Healey, S., Devereau, A., Hogervorst, F.B., Monteiro, A.N., Nathanson, K.L., Radice, P., Wappenschmidt, B., ENIGMA—Evidence-based network for the interpretation of germline mutant alleles: An international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes (2012) Hum. Mutat, 33, pp. 2-7; Schubert, S., van Luttikhuizen, J.L., Auber, B., Schmidt, G., Hofmann, W., Penkert, J., Davenport, C.F., Bublitz, J., The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants (2019) Int. J. Cancer, 144, pp. 2683-2694; Janavicius, R., Rudaitis, V., Feng, B.J., Ozolina, S., Griskevicius, L., Goldgar, D., Tihomirova, L., Haplotype analysis and ancient origin of the BRCA1 c.4035delA Baltic founder mutation (2013) Eur. J. Med. Genet., 56, pp. 125-130; Janavicius, R., Rudaitis, V., Mickys, U., Elsakov, P., Griskevicius, L., Comprehensive BRCA1 and BRCA2 mutational profile in Lithuania (2014) Cancer Genet, 207, pp. 195-205
PY - 2020
Y1 - 2020
N2 - 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
AB - 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
KW - Breast cancer predisposition
KW - Breast cancer risk factors
KW - FANCM truncating variants
KW - Mutation spectrum
KW - PTVs
KW - adult
KW - aged
KW - Article
KW - controlled study
KW - Czech Republic
KW - Denmark
KW - estrogen receptor negative breast cancer
KW - estrogen receptor positive breast cancer
KW - FANCM gene
KW - female
KW - Finland
KW - France
KW - gene
KW - gene frequency
KW - gene sequence
KW - genetic association
KW - genetic variability
KW - Greece
KW - human
KW - Hungary
KW - Lithuania
KW - major clinical study
KW - middle aged
KW - Poland
KW - Portugal
KW - protein truncating variant
KW - Spain
KW - Sweden
KW - tumor suppressor gene
KW - very elderly
U2 - 10.3390/cancers12020292
DO - 10.3390/cancers12020292
M3 - Article
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
ER -