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

RØYRVIK ET AL.Another topic that deserves attention is the functional consequence of mutationof mutated target gene expression. Both on the transcriptomic and proteomiclevels, a large-scale approach to this area would be useful in understanding therole of MSI in oncogenesis.Considering the comparative wealth of untested putative MMR target genesamong cMNR-containing sequences alone, not to mention those harboring diandtrinucleotide or repeats in UTRs and introns, it seems clear that a highthroughputapproach to analysis is desirable. Ideally, if somewhat unrealistically,all potential targets—both those that have been assessed in MSI tumors and thosethat have not—should be evaluated for a large consecutive clinical series.In short, after 12 years of research into targeted genes of mismatch repair deficientcolorectal cancers, we believe that those identified scarcely constituteeven the tip of the iceberg.REFERENCES1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics,2006. CA Cancer J Clin. 2006;56:106–30.2. Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin.Science. 2005;307(5717):1904–9.3. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell.1990;61:759–67.4. Grady WM. Genomic instability and colon cancer. Cancer Metastasis Rev.2004;23:11–27.5. Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194(4260):23–8.6. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers.Nature. 1998;396(6712):643–9.7. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, BurtRW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S. ANational Cancer Institute workshop on microsatellite instability for cancer detectionand familial predisposition: development of international criteria for thedetermination of microsatellite instability in colorectal cancer. Cancer Res.1998;58:5248–57.8. Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers.Nature. 1997;386(6625):623–7.9. Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C. The significance ofunstable chromosomes in colorectal cancer. Nat Rev Cancer. 2003;3:695–701.242