caa a22 4500 445331062 CHVBK 20180317142737.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10689-011-9461-y doi (NATIONALLICENCE)springer-10.1007/s10689-011-9461-y Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals [Elektronische Daten] [Mev Valentin, Felipe Silva, Erika Santos, Bianca Lisboa, Ligia de Oliveira, Fabio Ferreira, Israel Gomy, Wilson Nakagawa, Samuel Aguiar Junior, Mariana Redal, Carlos Vaccaro, Adriana Valle, Carlos Sarroca, Dirce Carraro, Benedito Rossi] Lynch syndrome (LS) is an autosomal dominant syndrome that predisposes individuals to development of cancers early in life. These cancers are mainly the following: colorectal, endometrial, ovarian, small intestine, stomach and urinary tract cancers. LS is caused by germline mutations in DNA mismatch repair genes (MMR), mostly MLH1 and MSH2, which are responsible for more than 85% of known germline mutations. To search for germline mutations in MLH1 and MSH2 genes in 123 unrelated South American suspected LS patients (Bethesda or Amsterdam Criteria) DNA was obtained from peripheral blood, and PCR was performed followed by direct sequencing in both directions of all exons and intron-exon junctions regions of the MLH1 and MSH2 genes. MLH1 or MSH2 pathogenic mutations were found in 28.45% (34/123) of the individuals, where 25/57 (43.85%) fulfilled Amsterdam I, II and 9/66 (13.63%) the Bethesda criteria. The mutations found in both genes were as follows: nonsense (35.3%), frameshift (26.47%), splicing (23.52%), and missense (9%). Thirteen alterations (35.14%) were described for the first time. The data reported in this study add new information about MLH1 and MSH2 gene mutations and contribute to better characterize LS in Brazil, Uruguay and Argentina. The high rate of novel mutations demonstrates the importance of defining MLH1 and MSH2 mutations in distinct LS populations. Springer Science+Business Media B.V., 2011 Lynch syndrome nationallicence MSH2 nationallicence MLH1 nationallicence MMR genes nationallicence Mutation nationallicence Valentin Mev Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut Silva Felipe Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut Santos Erika MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut Lisboa Bianca Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut de Oliveira Ligia Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut Ferreira Fabio MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut Gomy Israel Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut Nakagawa Wilson MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut Aguiar Junior Samuel MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut Redal Mariana Coloproctology Department, Hospital Italiano, Buenos Aires, Argentina aut Vaccaro Carlos Director of Hereditary Cancer Program, Hospital Italiano, Buenos Aires, Argentina aut Valle Adriana Hospital de las Fuerzas Armadas, Montevideo, Uruguay aut Sarroca Carlos Hospital de las Fuerzas Armadas, Montevideo, Uruguay aut Carraro Dirce Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut Rossi Benedito MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut Familial Cancer Springer Netherlands 10/4(2011-12-01), 641-647 1389-9600 10:4<641 2011 10 10689 https://doi.org/10.1007/s10689-011-9461-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9461-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Valentin Mev Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Silva Felipe Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Santos Erika MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Lisboa Bianca Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- de Oliveira Ligia Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Ferreira Fabio MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Gomy Israel Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Nakagawa Wilson MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Aguiar Junior Samuel MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Redal Mariana Coloproctology Department, Hospital Italiano, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Vaccaro Carlos Director of Hereditary Cancer Program, Hospital Italiano, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Valle Adriana Hospital de las Fuerzas Armadas, Montevideo, Uruguay aut NATIONALLICENCE 700 1- Sarroca Carlos Hospital de las Fuerzas Armadas, Montevideo, Uruguay aut NATIONALLICENCE 700 1- Carraro Dirce Laboratory of Genomics and Molecular Biology, Centro Internacional de Pesquisa e Ensino (CIPE), A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Rossi Benedito MsC/PhD Program, A.C.Camargo Hospital, São Paulo, Brazil aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/4(2011-12-01), 641-647 1389-9600 10:4<641 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer