Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility

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Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility. / Catucci, Irene; Osorio, Ana; Arver, Brita; Neidhardt, Guido; Bogliolo, Massimo; Zanardi, Federica; Riboni, Mirko; Minardi, Simone; Pujol, Roser; Azzollini, Jacopo; Peissel, Bernard; Manoukian, Siranoush; De Vecchi, Giovanna; Casola, Stefano; Hauke, Jan; Richters, Lisa; Rhiem, Kerstin; Schmutzler, Rita K; Wallander, Karin; Törngren, Therese; Borg, Åke; Radice, Paolo; Surrallés, Jordi; Hahnen, Eric; Ehrencrona, Hans; Kvist, Anders; Benitez, Javier; Peterlongo, Paolo.

I: Genetics in Medicine, Vol. 20, 2018, s. 452–457.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Catucci, I, Osorio, A, Arver, B, Neidhardt, G, Bogliolo, M, Zanardi, F, Riboni, M, Minardi, S, Pujol, R, Azzollini, J, Peissel, B, Manoukian, S, De Vecchi, G, Casola, S, Hauke, J, Richters, L, Rhiem, K, Schmutzler, RK, Wallander, K, Törngren, T, Borg, Å, Radice, P, Surrallés, J, Hahnen, E, Ehrencrona, H, Kvist, A, Benitez, J & Peterlongo, P 2018, 'Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility', Genetics in Medicine, vol. 20, s. 452–457. https://doi.org/10.1038/gim.2017.123

APA

CBE

Catucci I, Osorio A, Arver B, Neidhardt G, Bogliolo M, Zanardi F, Riboni M, Minardi S, Pujol R, Azzollini J, Peissel B, Manoukian S, De Vecchi G, Casola S, Hauke J, Richters L, Rhiem K, Schmutzler RK, Wallander K, Törngren T, Borg Å, Radice P, Surrallés J, Hahnen E, Ehrencrona H, Kvist A, Benitez J, Peterlongo P. 2018. Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility. Genetics in Medicine. 20:452–457. https://doi.org/10.1038/gim.2017.123

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Author

Catucci, Irene ; Osorio, Ana ; Arver, Brita ; Neidhardt, Guido ; Bogliolo, Massimo ; Zanardi, Federica ; Riboni, Mirko ; Minardi, Simone ; Pujol, Roser ; Azzollini, Jacopo ; Peissel, Bernard ; Manoukian, Siranoush ; De Vecchi, Giovanna ; Casola, Stefano ; Hauke, Jan ; Richters, Lisa ; Rhiem, Kerstin ; Schmutzler, Rita K ; Wallander, Karin ; Törngren, Therese ; Borg, Åke ; Radice, Paolo ; Surrallés, Jordi ; Hahnen, Eric ; Ehrencrona, Hans ; Kvist, Anders ; Benitez, Javier ; Peterlongo, Paolo. / Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility. I: Genetics in Medicine. 2018 ; Vol. 20. s. 452–457.

RIS

TY - JOUR

T1 - Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility

AU - Catucci, Irene

AU - Osorio, Ana

AU - Arver, Brita

AU - Neidhardt, Guido

AU - Bogliolo, Massimo

AU - Zanardi, Federica

AU - Riboni, Mirko

AU - Minardi, Simone

AU - Pujol, Roser

AU - Azzollini, Jacopo

AU - Peissel, Bernard

AU - Manoukian, Siranoush

AU - De Vecchi, Giovanna

AU - Casola, Stefano

AU - Hauke, Jan

AU - Richters, Lisa

AU - Rhiem, Kerstin

AU - Schmutzler, Rita K

AU - Wallander, Karin

AU - Törngren, Therese

AU - Borg, Åke

AU - Radice, Paolo

AU - Surrallés, Jordi

AU - Hahnen, Eric

AU - Ehrencrona, Hans

AU - Kvist, Anders

AU - Benitez, Javier

AU - Peterlongo, Paolo

PY - 2018

Y1 - 2018

N2 - PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations.MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes.ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene.ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.Genetics in Medicine advance online publication, 24 August 2017; doi:10.1038/gim.2017.123.

AB - PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations.MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes.ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene.ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.Genetics in Medicine advance online publication, 24 August 2017; doi:10.1038/gim.2017.123.

U2 - 10.1038/gim.2017.123

DO - 10.1038/gim.2017.123

M3 - Article

VL - 20

SP - 452

EP - 457

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

ER -