Author/Editor		Hudler, Petra
Title		Genetic testing, an optimal strategy for lynch syndrome identification
Type		članek
Source		5234202
Publication year		2013
Volume		str. 63-83
Language		eng
Abstract		During the last few decades, cancer genomics has facilitated the discovery of underlying causes implicated in the development of hereditary colorectal syndromes, such as Lynch syndrome. This heterogeneous disease usually arises as the consequence of germline mutations in DNA mismatch repair (MMR) genes. The most prominent feature of defective MMR system is genomic instability, which is manifested as microsatellite instability (MSI) in more than 90 % of Lynch-syndrome associated cancers. Molecular characterization of MSI by fragment analysis and absence of MMR proteins by immunohistochemistry (IHC) in tumor tissues is useful for selecting at-risk patients who might be carriers of mutations in MMR genes or EPCAM. EPCAM is epithelial cell adhesion molecule gene, which, when mutated, affects the translation of MMR gene MSH2. The diagnosis in these case s is confirmed by identifying the mutation uti lizing sequencing or other sequence detection methods or testing for large deletions and rearrangements of MMR genes. Clinical management of confirmed Lynch syndrome patients differs from those with sporadic colorectal cancers and also offers an opportunity to provide predictive screening for family members to determine mutation carriers. Susceptible members are offered regular c1inical surveillance, which is beneficial for early diagnosis of colorectal and endometrial cancers and in reducing cancer morbidity. Despite the complexity of molecul~r diagnostic procedure, it is the most accurate diagnostic method for identifying patients with Lynch syndrome. In the future, the advances in next-generation sequencing methods and instrumentation could provide even more accurate and straightforward diagnostic modality due to simultaneous detection of mutations, large deletions, chromosome rearrangements and copy number variations using different library preparation methods and sequencing approaches.
Keywords		genetic testing genomic instability Lynch syndrome gensko testiranje genomska nestabilnost Lynch sindrom