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

Research output: Contribution to journalArticle


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.


  • Mev Dominguez
  • Felipe Carneiro da Silva
  • Erika Maria Monteiro dos Santos
  • Bianca Garcia Lisboa
  • Ligia Petrolini de Oliveira
  • Fabio de Oliveira Ferreira
  • Israel Gomy
  • Wilson Toshihiko Nakagawa
  • Samuel Aguiar Junior
  • Mariana Redal
  • Carlos Vaccaro
  • Adriana Della Valle
  • Carlos Sarroca
  • Dirce Maria Carraro
  • Benedito Mauro Rossi
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • Lynch syndrome, MSH2, MLH1, MMR genes, Mutation
Original languageEnglish
Pages (from-to)641-647
JournalFamilial Cancer
Issue number4
Publication statusPublished - 2011
Publication categoryResearch