RESUMO
Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary syndrome with genetic heterogeneity. The disease is caused by mutations or epigenetic silencing in DNA mismatch repair genes, MLH1, MSH2, MSH6, PMS2 and MLH3, although the vast majority of cases correspond to mutations of MLH1 and MSH2. We herein describe a nucleotide change, c.2063T>G in exon 13 of the MSH2 gene, present in families that fulfill the Amsterdam criteria for Lynch syndrome and originate from northern Tenerife (Canary Islands-Spain). This mutation is expected to result in a nonconservative amino acid change, M688R, at the ATPase domain of the MSH2 protein. We found five large families with this mutation, and about half the individuals heterozygous for M688R developed malignancies by the sixth decade of life. In many cases analyzed, their tumors revealed loss of the normal allele, being homozygous for M688R. There is an evidence of historical isolation for the population studied, which could have favored a considerable genetic drift. The presence of the same mutation and the disease associated-haplotype conservation in families not directly related can be probably the consequence of a bottleneck in the founding of this population (rather than a relatively recent founding of the mutation).
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Efeito Fundador , Proteína 2 Homóloga a MutS/genética , Mutação , Reparo de Erro de Pareamento de DNA , Feminino , Haplótipos/genética , Homozigoto , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , EspanhaRESUMO
Catheter-related infection in cancer patients remains an important health-care problem with major financial implications. During the last few years a better understanding of the pathogenesis of catheter-related infections and the interaction between microorganisms and catheter surfaces has emerged. Recently the influence of biofilm formation in catheter-related infections has been established. The development of biofilm by the colonizing microbes permits attachment of the organisms to the vascular access device and confers resistance to antibiotics and host defense mechanisms. Strategies to overcome the development of biofilm are being developed to prevent catheter- and other medical device-related infections.