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Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals

Dominguez, Mev LU ; da Silva, Felipe Carneiro; Monteiro dos Santos, Erika Maria; Lisboa, Bianca Garcia; de Oliveira, Ligia Petrolini; Ferreira, Fabio de Oliveira; Gomy, Israel; Nakagawa, Wilson Toshihiko; Aguiar Junior, Samuel and Redal, Mariana, et al. (2011) In Familial Cancer 10(4). p.641-647
Abstract
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... (More)
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. (Less)
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published
subject
keywords
Lynch syndrome, MSH2, MLH1, MMR genes, Mutation
in
Familial Cancer
volume
10
issue
4
pages
641 - 647
publisher
Kluwer
external identifiers
  • wos:000301507900003
  • scopus:84855685053
ISSN
1389-9600
DOI
10.1007/s10689-011-9461-y
language
English
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yes
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9c505d7f-574b-4eac-8e27-5bfbd640f036 (old id 2493635)
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2012-05-08 08:35:45
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2017-09-24 03:20:43
@article{9c505d7f-574b-4eac-8e27-5bfbd640f036,
  abstract     = {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.},
  author       = {Dominguez, Mev and da Silva, Felipe Carneiro and Monteiro dos Santos, Erika Maria and Lisboa, Bianca Garcia and de Oliveira, Ligia Petrolini and Ferreira, Fabio de Oliveira and Gomy, Israel and Nakagawa, Wilson Toshihiko and Aguiar Junior, Samuel and Redal, Mariana and Vaccaro, Carlos and Della Valle, Adriana and Sarroca, Carlos and Carraro, Dirce Maria and Rossi, Benedito Mauro},
  issn         = {1389-9600},
  keyword      = {Lynch syndrome,MSH2,MLH1,MMR genes,Mutation},
  language     = {eng},
  number       = {4},
  pages        = {641--647},
  publisher    = {Kluwer},
  series       = {Familial Cancer},
  title        = {Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals},
  url          = {http://dx.doi.org/10.1007/s10689-011-9461-y},
  volume       = {10},
  year         = {2011},
}