The pathogenesis of microsatellite unstable colorectal cancer and the evaluation of novel diagnostic and therapeutic options
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Beschreibung
Colorectal cancer (CRC) is a disease with a heterogeneous molecular pathogenesis. Insight into the molecular alterations that contribute to the development of CRC provides us with novel parameters for cancer classification and paves the way for new targeted therapies. Whereas the majority of CRCs are characterized by large genomic rearrangements and the inactivation of tumor suppressor genes, following the classical adenoma-carcinoma model, a subset of CRCs is caused by inactivation of the DNA mismatch repair (MMR) system that leads to the accumulation of numerous small insertion/deletion mutations, with a predominance of mutations that affect short repetitive DNA stretches termed microsatellites (Figure 1). Microsatellites are short repetitions of single nucleotides (mononucleotide repeats), or stretches composed of more complex repeat units consisting of two, three, four (di-, tri-, tetranucleotide repeats) or more nucleotides. The phenotype of genetic instability resulting from MMR deficiency is termed high level microsatellite instability (MSI-H) and describes the abundance of length alterations at microsatellites spread over the whole genome. The present thesis will deal with the molecular pathogenesis of MSI-H cancers and novel diagnostic and therapeutic options derived from the molecular events involved in MSI-H tumor development.
Autor*in
Matthias Johannes Kloor
Themen in »The pathogenesis of microsatellite unstable colorectal cancer and the evaluation of novel diagnostic and therapeutic options«
HNPCC Lynch syndrome colorectal cancer microsatellite instability tumor immunology