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

Introduction“Epigenetic inheritance is the transmission ofinformation from a cell or multicellular organism to itsdescendants without that information being encoded inthe nucleotide sequence of the gene.”Cancer as a genetic and epigenetic diseaseThere are innumerable components in the human cells involved in keeping close control onhomeostasis, and a very simplistic view on cancer is that it is a disease caused by a skewedratio in proliferation and apoptosis, favoring cell proliferation[9]. It does not need to be ahuge growth-advantage in order to abolish homeostasis and cause transformed cells to takeover the population. An 1% increase in the proliferation-apoptosis ratio will cause theaffected cell to go from 0.001% to 99.9% of the population in 5 years given that the celldivides every 24 hours[10]. This illustrates the theory of clonal expansion which say thatincreased fitness of a cell will lead to clonal selection[11]. The growth advantage can occurby various mechanisms, and six hallmarks which cancer cells must acquire in order to reachmalignancy has been suggested, including resistance to apoptosis, self-sufficiency in growthsignals, insensitivity to anti-growth signals, limitless replicative potential, sustainedangiogenesis, and tissue invasion and metastasis[12] (Figure 1).Figure 1. Biology of cancer. (A) Most cancers are believed to undergo a clonal expansion. The genetic orepigenetic events may be of any kind giving the cell a selective advantage. (B) Ultimately, these changes mayfulfill Hanahan and Weinberg’s six hallmarks of cancer. Courtesy of RI Skotheim.12