RESUMO
BACKGROUND: A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. METHODS: Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. RESULTS AND CONCLUSION: A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fusion transcripts between MLH1 and LRRFIP2. A single-nucleotide polymorphism in MLH1 exon 8 was expressed from both alleles, initially pointing to appropriate MLH1 function at least in peripheral cells. In a second case, an inherited duplication of the MLH1 gene region resulted in constitutional MLH1 promoter methylation. Constitutional MLH1 promoter methylation may therefore in rare cases be a heritable disease mechanism and should not be overlooked in seemingly sporadic patients.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Metilação de DNA/genética , DNA Complementar/genética , Rearranjo Gênico/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas , Alelos , Sequência de Bases , Inversão Cromossômica/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Análise Mutacional de DNA , Éxons/genética , Família , Feminino , Duplicação Gênica/genética , Testes Genéticos , Genoma Humano/genética , Humanos , Masculino , Dados de Sequência Molecular , Proteína 1 Homóloga a MutL , LinhagemRESUMO
We investigated whether a novel monoclonal stool antigen test for detection of Helicobacter pylori performs with the same accuracy as the (13)C-urea breath test (UBT) for adult outpatients in the setting of a private office. The two tests showed identical levels of sensitivity when used to identify H. pylori-infected patients before and after eradication therapy.
