International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation

Ana Peixoto; Catarina Santos; Manuela Pinheiro; Pedro Pinto; Maria José Soares; Patrícia Rocha; Leonor Gusmão; António Amorim; Annemarie Van Der Hout; Anne Marie Gerdes; Mads Thomassen; Torben A. Kruse; Dorthe Cruger; Lone Sunde; Yves Jean Bignon; Nancy Uhrhammer; Lucie Cornil; Etienne Rouleau; Rosette Lidereau; Drakoulis Yannoukakos; Maroulio Pertesi; Steven Narod; Robert Royer; Maurício M. Costa; Conxi Lazaro; Lidia Feliubadaló; Begoña Graña; Ignacio Blanco; Miguel De La Hoya; Trinidad Caldés; Philippe Maillet; Gaelle Benais-Pont; Bruno Pardo; Yael Laitman; Eitan Friedman; Eladio A. Velasco; Mercedes Durán; Maria Dolores Miramar; Ana Rodriguez Valle; María Teresa Calvo; Ana Vega; Ana Blanco; Orland Diez; Sara Gutiérrez-Enríquez; Judith Balmaña; Teresa Ramon Y Cajal; Carmen Alonso; Montserrat Baiget; William Foulkes; Marc Tischkowitz; Rachel Kyle; Nelly Sabbaghian; Patricia Ashton-Prolla; Ingrid P. Ewald; Thangarajan Rajkumar; Luisa Mota-Vieira; Giuseppe Giannini; Alberto Gulino; Maria I. Achatz; Dirce M. Carraro; Brigitte Bressac De Paillerets; Audrey Remenieras; Cindy Benson; Silvia Casadei; Mary Claire King; Erik Teugels; Manuel R. Teixeira

doi:10.1007/s10549-010-1036-3

International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation

Ana Peixoto, Catarina Santos, Manuela Pinheiro, Pedro Pinto, Maria José Soares, Patrícia Rocha, Leonor Gusmão, António Amorim, Annemarie Van Der Hout, Anne Marie Gerdes, Mads Thomassen, Torben A. Kruse, Dorthe Cruger, Lone Sunde, Yves Jean Bignon, Nancy Uhrhammer, Lucie Cornil, Etienne Rouleau, Rosette Lidereau, Drakoulis YannoukakosMaroulio Pertesi, Steven Narod, Robert Royer, Maurício M. Costa, Conxi Lazaro, Lidia Feliubadaló, Begoña Graña, Ignacio Blanco, Miguel De La Hoya, Trinidad Caldés, Philippe Maillet, Gaelle Benais-Pont, Bruno Pardo, Yael Laitman, Eitan Friedman, Eladio A. Velasco, Mercedes Durán, Maria Dolores Miramar, Ana Rodriguez Valle, María Teresa Calvo, Ana Vega, Ana Blanco, Orland Diez, Sara Gutiérrez-Enríquez, Judith Balmaña, Teresa Ramon Y Cajal, Carmen Alonso, Montserrat Baiget, William Foulkes, Marc Tischkowitz, Rachel Kyle, Nelly Sabbaghian, Patricia Ashton-Prolla, Ingrid P. Ewald, Thangarajan Rajkumar, Luisa Mota-Vieira, Giuseppe Giannini, Alberto Gulino, Maria I. Achatz, Dirce M. Carraro, Brigitte Bressac De Paillerets, Audrey Remenieras, Cindy Benson, Silvia Casadei, Mary Claire King, Erik Teugels, Manuel R. Teixeira

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

The c.156-157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156-157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156-157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.

Original language	English
Pages (from-to)	671-679
Number of pages	9
Journal	Breast Cancer Research and Treatment
Volume	127
Issue number	3
DOIs	https://doi.org/10.1007/s10549-010-1036-3
State	Published - Jun 2011
Externally published	Yes

Funding

Funders	Funder number
Susan G. Komen
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Hospital de Clínicas de Porto Alegre
Ministerio de Ciencia e Innovación	200820I135
Comisión Sectorial de Investigación Científica
Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção
Liga Portuguesa Contra o Cancro
Administração Regional de Saúde do Norte, Ministério da Saúde	15/2007

Keywords

Age estimation
Founder mutation
Hereditary breast/ovarian cancer
c.156-157insAlu BRCA2 mutation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10549-010-1036-3

Cite this

Peixoto, A., Santos, C., Pinheiro, M., Pinto, P., Soares, M. J., Rocha, P., Gusmão, L., Amorim, A., Van Der Hout, A., Gerdes, A. M., Thomassen, M., Kruse, T. A., Cruger, D., Sunde, L., Bignon, Y. J., Uhrhammer, N., Cornil, L., Rouleau, E., Lidereau, R., ... Teixeira, M. R. (2011). International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation. Breast Cancer Research and Treatment, 127(3), 671-679. https://doi.org/10.1007/s10549-010-1036-3

@article{86a1bf60fe1e48a680c2a398e6c86d3b,

title = "International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation",

abstract = "The c.156-157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156-157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9\% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156-157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.",

keywords = "Age estimation, Founder mutation, Hereditary breast/ovarian cancer, c.156-157insAlu BRCA2 mutation",

author = "Ana Peixoto and Catarina Santos and Manuela Pinheiro and Pedro Pinto and Soares, \{Maria Jos{\'e}\} and Patr{\'i}cia Rocha and Leonor Gusm{\~a}o and Ant{\'o}nio Amorim and \{Van Der Hout\}, Annemarie and Gerdes, \{Anne Marie\} and Mads Thomassen and Kruse, \{Torben A.\} and Dorthe Cruger and Lone Sunde and Bignon, \{Yves Jean\} and Nancy Uhrhammer and Lucie Cornil and Etienne Rouleau and Rosette Lidereau and Drakoulis Yannoukakos and Maroulio Pertesi and Steven Narod and Robert Royer and Costa, \{Maur{\'i}cio M.\} and Conxi Lazaro and Lidia Feliubadal{\'o} and Bego{\~n}a Gra{\~n}a and Ignacio Blanco and \{De La Hoya\}, Miguel and Trinidad Cald{\'e}s and Philippe Maillet and Gaelle Benais-Pont and Bruno Pardo and Yael Laitman and Eitan Friedman and Velasco, \{Eladio A.\} and Mercedes Dur{\'a}n and Miramar, \{Maria Dolores\} and Valle, \{Ana Rodriguez\} and Calvo, \{Mar{\'i}a Teresa\} and Ana Vega and Ana Blanco and Orland Diez and Sara Guti{\'e}rrez-Enr{\'i}quez and Judith Balma{\~n}a and \{Ramon Y Cajal\}, Teresa and Carmen Alonso and Montserrat Baiget and William Foulkes and Marc Tischkowitz and Rachel Kyle and Nelly Sabbaghian and Patricia Ashton-Prolla and Ewald, \{Ingrid P.\} and Thangarajan Rajkumar and Luisa Mota-Vieira and Giuseppe Giannini and Alberto Gulino and Achatz, \{Maria I.\} and Carraro, \{Dirce M.\} and \{De Paillerets\}, \{Brigitte Bressac\} and Audrey Remenieras and Cindy Benson and Silvia Casadei and King, \{Mary Claire\} and Erik Teugels and Teixeira, \{Manuel R.\}",

note = "Funding Information: Acknowledgments This study was supported by Minist{\'e}rio da Sa{\'u}de (Project N° 15/2007) and Liga Portuguesa Contra o Cancro. IPATIMUP was funded by Fundac¸{\~a}o para a Ci{\^e}ncia e Tecnologia, through POCI (Programa Operacional Ci{\^e}ncia e Inovac¸{\~a}o 2010). MT and WDF are supported by the Susan G. Komen Foundation for the Funding Information: Cure, the Jewish General Hospital Weekend to End Breast Cancer and the Fonds de la Recherche en Sant{\'e} du Qu{\'e}bec. EAV and MD are supported by grants PI061102 (Ministerio de Ciencia e Innovaci{\'o}n) and 200820I135 (CSIC). AV and AB thank Mar{\'i}a J. Magdalena for her excellent technical support at the Fundaci{\'o}n P{\'u}blica Galega de Medicina Xen{\'o}mica. PAP and IPE were supported by CNPq, CAPES, Fundac¸{\~a}o de Incentivo {\`a} Pesquisa do Hospital de Cl{\'i}nicas de Porto Alegre, and Rede Nacional de C{\^a}ncer Familial, Brazil. The authors declare that they have no conflict of interest.",

year = "2011",

month = jun,

doi = "10.1007/s10549-010-1036-3",

language = "אנגלית",

volume = "127",

pages = "671--679",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer",

number = "3",

}

Peixoto, A, Santos, C, Pinheiro, M, Pinto, P, Soares, MJ, Rocha, P, Gusmão, L, Amorim, A, Van Der Hout, A, Gerdes, AM, Thomassen, M, Kruse, TA, Cruger, D, Sunde, L, Bignon, YJ, Uhrhammer, N, Cornil, L, Rouleau, E, Lidereau, R, Yannoukakos, D, Pertesi, M, Narod, S, Royer, R, Costa, MM, Lazaro, C, Feliubadaló, L, Graña, B, Blanco, I, De La Hoya, M, Caldés, T, Maillet, P, Benais-Pont, G, Pardo, B, Laitman, Y, Friedman, E, Velasco, EA, Durán, M, Miramar, MD, Valle, AR, Calvo, MT, Vega, A, Blanco, A, Diez, O, Gutiérrez-Enríquez, S, Balmaña, J, Ramon Y Cajal, T, Alonso, C, Baiget, M, Foulkes, W, Tischkowitz, M, Kyle, R, Sabbaghian, N, Ashton-Prolla, P, Ewald, IP, Rajkumar, T, Mota-Vieira, L, Giannini, G, Gulino, A, Achatz, MI, Carraro, DM, De Paillerets, BB, Remenieras, A, Benson, C, Casadei, S, King, MC, Teugels, E & Teixeira, MR 2011, 'International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation', Breast Cancer Research and Treatment, vol. 127, no. 3, pp. 671-679. https://doi.org/10.1007/s10549-010-1036-3

TY - JOUR

T1 - International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation

AU - Peixoto, Ana

AU - Santos, Catarina

AU - Pinheiro, Manuela

AU - Pinto, Pedro

AU - Soares, Maria José

AU - Rocha, Patrícia

AU - Gusmão, Leonor

AU - Amorim, António

AU - Van Der Hout, Annemarie

AU - Gerdes, Anne Marie

AU - Thomassen, Mads

AU - Kruse, Torben A.

AU - Cruger, Dorthe

AU - Sunde, Lone

AU - Bignon, Yves Jean

AU - Uhrhammer, Nancy

AU - Cornil, Lucie

AU - Rouleau, Etienne

AU - Lidereau, Rosette

AU - Yannoukakos, Drakoulis

AU - Pertesi, Maroulio

AU - Narod, Steven

AU - Royer, Robert

AU - Costa, Maurício M.

AU - Lazaro, Conxi

AU - Feliubadaló, Lidia

AU - Graña, Begoña

AU - Blanco, Ignacio

AU - De La Hoya, Miguel

AU - Caldés, Trinidad

AU - Maillet, Philippe

AU - Benais-Pont, Gaelle

AU - Pardo, Bruno

AU - Laitman, Yael

AU - Friedman, Eitan

AU - Velasco, Eladio A.

AU - Durán, Mercedes

AU - Miramar, Maria Dolores

AU - Valle, Ana Rodriguez

AU - Calvo, María Teresa

AU - Vega, Ana

AU - Blanco, Ana

AU - Diez, Orland

AU - Gutiérrez-Enríquez, Sara

AU - Balmaña, Judith

AU - Ramon Y Cajal, Teresa

AU - Alonso, Carmen

AU - Baiget, Montserrat

AU - Foulkes, William

AU - Tischkowitz, Marc

AU - Kyle, Rachel

AU - Sabbaghian, Nelly

AU - Ashton-Prolla, Patricia

AU - Ewald, Ingrid P.

AU - Rajkumar, Thangarajan

AU - Mota-Vieira, Luisa

AU - Giannini, Giuseppe

AU - Gulino, Alberto

AU - Achatz, Maria I.

AU - Carraro, Dirce M.

AU - De Paillerets, Brigitte Bressac

AU - Remenieras, Audrey

AU - Benson, Cindy

AU - Casadei, Silvia

AU - King, Mary Claire

AU - Teugels, Erik

AU - Teixeira, Manuel R.

N1 - Funding Information: Acknowledgments This study was supported by Ministério da Saúde (Project N° 15/2007) and Liga Portuguesa Contra o Cancro. IPATIMUP was funded by Fundac¸ão para a Ciência e Tecnologia, through POCI (Programa Operacional Ciência e Inovac¸ão 2010). MT and WDF are supported by the Susan G. Komen Foundation for the Funding Information: Cure, the Jewish General Hospital Weekend to End Breast Cancer and the Fonds de la Recherche en Santé du Québec. EAV and MD are supported by grants PI061102 (Ministerio de Ciencia e Innovación) and 200820I135 (CSIC). AV and AB thank María J. Magdalena for her excellent technical support at the Fundación Pública Galega de Medicina Xenómica. PAP and IPE were supported by CNPq, CAPES, Fundac¸ão de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre, and Rede Nacional de Câncer Familial, Brazil. The authors declare that they have no conflict of interest.

PY - 2011/6

Y1 - 2011/6

N2 - The c.156-157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156-157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156-157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.

AB - The c.156-157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156-157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156-157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.

KW - Age estimation

KW - Founder mutation

KW - Hereditary breast/ovarian cancer

KW - c.156-157insAlu BRCA2 mutation

UR - http://www.scopus.com/inward/record.url?scp=79958280483&partnerID=8YFLogxK

U2 - 10.1007/s10549-010-1036-3

DO - 10.1007/s10549-010-1036-3

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 20652400

AN - SCOPUS:79958280483

SN - 0167-6806

VL - 127

SP - 671

EP - 679

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -

International distribution and age estimation of the Portuguese BRCA2 c.156-157insAlu founder mutation

Abstract

Funding

Keywords

UN SDGs

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