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

DISCUSSIONColorectal cancer is a very common disease with a poor 5-year survival. Any finding whichaid in discriminating patients with a good versus poor prognosis will therefore have animpact on a large number of patients. Currently, tumor stage at time of diagnosis is the onlyparameter used in classifying patients into different categories, in which fit patients withstage III disease who will receive adjuvant chemotherapy.[15;16] Still, there are some patientswith a stage II disease who will experience recurrence, and who would benefit fromchemotherapy. On the other hand, some 50% of stage III patients will not recur aftersurgery alone and could be spared from the treatment related side-effects. With the aim offinding markers with prognostic potential in a low-risk group of colorectal cancer patients,we analyzed 41 genes with coding oligonucleotide repeats (all but one were mononucleotide)in two independent series of colorectal MSI tumors.This same approach has been performed in earlier studies, but in very small numbers of bothgenes and patients. Results are differing, some find mutations in both of TGFBR2 and BAXto be associated with poor prognosis,[17;18] another study finds them to be associated withan improved survival,[19;20] while some do not find any associations to survival at all.[21] Asmall study found that mutation in ATR showed a trend towards improved survival,although not significant.[22] A couple of studies have looked at protein expression of someof the genes included here in association to survival and found that low BAX expression isassociated with poor survival,[23] and that strong staining of RAD50/MRE11/NBS1 wasassociated with a favorable survival.[24] In order to include driver-genes that are likely tohave an impact on tumorigenesis in the study, strict selection criteria were employed.18