Suchergebnisse

<b>Objective:</b> Identification of clinical and molecular characteristics associated with constitutional <i>MLH1</i> and <i>MSH2</i> mutations and definition of a stepwise strategy for the selection of colorectal cancer (CRC) patients amenable to <i>MLH1</i> and <i>MSH2</i> genetic testing. <b>Methods:</b> 90 unrelated CRC patients were initially selected on the basis of either familial or early onset occurrence of CRC. They were screened for the presence of constitutional <i>MLH1</i> and <i>MSH2</i> mutations and for microsatellite instability (MSI). <b>Results:</b> 16 pathogenetic mutations (9 <i>MLH1</i> and 7 <i>MSH2</i>) were identified in 41% of Amsterdam hereditary nonpolyposis colorectal cancer (HNPCC) families, 5% of suspected HNPCC families, and 14% of sporadic early-onset CRC patients. The presence of the mutations correlated with MSI, with early age of onset and proximal location of the tumor, and with the presence of some extracolonic tumors of the HNPCC spectrum and/or multiple tumors in the family. <b>Conclusions:</b> Evaluation of clinical and molecular characteristics is useful for the identification of candidates to <i>MLH1</i> and <i>MSH2</i> mutational analysis and allows the application of a rational approach to genetic testing.