Novel genetic and epigenetic alterations in ... - Ous-research.no

Discussionchromosomes in metaphase[189], and loss of expression has been shown to cause G2/Marrest[190]. Indels in the 5’UTR region of this gene, a site of major translational regulation,may affect translational efficiency and stability, leading to cancer cell arrest and reducedproliferation. Knocking out RCC2 therefore seems like a bad strategy for a cancer cell, andone would expect a strong negative selection pressure. Still, we see a mutation frequencyabove 50%, indicating that this is not the case.Figure 15. Study sizesanalyzing coding repetitiveunits in MSI-tumors. Allstudies included in the reviewfrom 2007[90] are included.Sample size and number ofgenes analyzed are plottedagainst each other. Moststudies analyze a small numberof samples for a restrictednumber of genes. The starindicates the size of the studypresented in paper IV.Predictive markersWhile some biomarkers are well suited for diagnostic purposes, others can be used todetermine, or predict, response to a certain therapy. Such markers are called predictivemarkers. In paper III we showed that mutations in KRAS and BRAF were common in CRCas they were present in 62% of the tumors. Mutations in these genes have in other studiesbeen shown to predict response to cetuximab, a monoclonal antibody therapy targeting theepidermal growth factor receptor (EGFR). About 30-40% of non-responders to this therapycarry a KRAS mutation. Mutations in BRAF is significantly associated with lack of treatmentresponse as none of the patients with BRAF mut responded, while none of the responders58