In this work we describe in detail the problems associated with the detection of specific molecular biomarkers of cancer. Determination of markers in complex heterogeneous diseases such as cancer of the stomach, requires a multi-stage approach involving the detection of changes at the level of DNA or RNA, followed by, where possible, the development of a simple and robust proteomic methods that could be useful in routine diagnosis.
COBISS.SI-ID: 31054297
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 cases is confirmed by identifying the mutation utilizing 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 clinical surveillance, which is beneficial for early diagnosis of colorectal and endometrial cancers and in reducing cancer morbidity. Despite the complexity of molecular 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.
COBISS.SI-ID: 30751961
This review focuses on advances in classical proteomic approaches and emerging high-throughput proteomic technologies for identifying cancer biomarkers. It is thus an indirect result of this project. However, in research on identification the molecular basis of malignancy a combination of biomarrkers at genomic / transcriptomic level (which is the focus of this project) and at proteomic level may at present be the best choice for the research as well as for diagnostics.
COBISS.SI-ID: 30290393