Suchergebnisse

<b><i>Background:</i></b> Lynch syndrome (LS) is the most frequent form of hereditary colorectal cancer (CRC; up to 3–5% of the total CRC burden) and predisposes to the development of other cancers. Multidisciplinary diagnostic strategies are relevant both to the index cases and to their at-risk relatives, but their implementation is still limited. Our study aimed to explore LS testing practices in Italy. <b><i>Methods:</i></b> In order to ascertain the current practice of LS diagnosis and management, we conducted a qualitative assessment by sending a questionnaire to health care professionals at 4 Italian hospitals selected as "models" representing different hospital settings. Based on the surveys, we reconstructed the management pathways for CRC patients in terms of diagnostic strategies and health professionals involved. <b><i>Results:</i></b> Seven of the 8 invited professionals filled in the questionnaire. Noncompliance with the latest guidelines was reported, as no tumor "screening" was performed on CRC cases. The lack of a structured multidisciplinary team who manages CRC patients from risk assessment to diagnosis and follow-up was reported. The availability of professionals and laboratory technologies differ widely between hospitals. As for cascade testing of at-risk relatives, a systematic and active approach was absent in all the considered hospitals. <b><i>Conclusions:</i></b> Our study shows that no structured and standardized pathways for the diagnosis and management of LS patients are currently in place in Italy. We envisage that by extending our research to further experiences and countries, an increasing awareness of the topic can be translated into a health gain for hereditary CRC patients and their at-risk relatives.

<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.

In 2013, the American College of Medical Genetics (ACMG) examined the issue of incidental findings in whole exome and whole genome sequencing, and introduced recommendations to search for, evaluate and report medically actionable variants in a set of 56 genes. At a debate held during the 2014 European Society for Human Genetics Conference (ESHG) in Milan, Italy, the first author of that paper presented this view in a debate session that did not end with a conclusive vote from the mainly European audience for or against reporting back actionable incidental findings. In this meeting report, we elaborate on the discussions held during a special meeting hosted at the ESHG in 2013 from posing the question 'How to reach a (European) consensus on reporting incidental findings and unclassified variants in diagnostic next generation sequencing'. We ask whether an European consensus exists on the reporting of incidental findings in genome diagnostics, and present a series of key issues that require discussion at both a national and European level in order to develop recommendations for handling incidental findings and unclassified variants in line with the legal and cultural particularities of individual European member states.