3. Detection of Patients with Microsatellite Instability Phenotype
CRC can be molecularly divided into two major subgroups, microsatellite-stable (MSS, ~85%) and microsatellite-instable (MSI, ~15%) CRCs. CRC patients presenting MSI have a better prognosis associated with a longer overall survival and a more benign disease course but their tumors are resistant to a wide range of chemotherapeutics [14,15]. Genes that correlate with MSI status were identified using full-genome expression data [16]. Subsequently, a MSI gene expression signature of 64 genes was developed and translated to a diagnostic microarray. This signature was able to identify patients with MSI status with high accuracy and additionally MSI-like patients who are not recognized by traditional methods like PCR or immunohistochemistry (IHC) [16]. The 64-gene signature owns some more advantages compared to PCR or IHC, i.e., robust and reproducible measurements, the signature can be read out from the same tissue biopsy and does not require a comparison of regions from paired normal and tumor tissue [16]. The MS status of CRC could be also correctly predicted based on miRNA expression profiles. Spotted locked nucleic acid (LNA)-based oligonucleotide microarrays were used to profile the expression of 315 miRNAs [17]. Therefore, miRNAs may also be potentially used to classify colon cancers as either MSI or MSS.