Conceptual evolution in cancer biology

Abstract

Stem cells are founder cells for every organ, tissue, and cell type in the body. Epigenetic processes govern cell differentiation by turning on or off tissue-specific genes; it also is an important mechanism of tumorigenesis. The major epigenetic process operates through DNA methylation at CpG sites converting cytosine to 5-methylcytosine. Another epigenetic process, gene imprinting, causes parental allele-specific expression of genes and is required in the development of an embryo. Loss of imprinting is associated with many types of tumors. DNA homeostasis depends on DNA repair. Impaired DNA mismatch repair mechanisms in the cell lead to accumulation of nonrepairable DNA alterations such as microsatellite instability, which is associated with both hereditary nonpolyposis colorectal cancer and sporadic colorectal cancers. Chromosome instability leads to changes of number and structure of chromosomes, including chromosomal losses, gains, and rearrangements. These are common features of malignant tumors. Gene expression is also regulated posttranscriptionally through microRNA or RNAi, which degrade the mRNA through binding to its complementary sequence. Telomeres protect the chromosome from gene loss by preventing ring chromosome formation and from gene gain by eliminating nonreciprocal translocation during cell division.