Clonality: Molecular criteria and clinical utility
Conceptually, a clone is a group of genetically identical cells derived from a single common ancestor Most somatic tissues arc polyclonal, unless there is a significant growth advantage within a subset of cells which proliferate at the expense of surrounding cells. Clonal proliferation in most somatic tissues may be viewed as evidence of the creation of a cell or group of cells with a growth advantage Clonal derivation of cells is a hallmark of neoplasia, and strongly implicates acquired somatic mutations giving proliferative advantage to a given clonal cell population
There are several tested methods to determine clonality. Karyotypic alterations common to all cells of a tumor confirm clonal origin, but require fresh unfixed tissue with viable cells, a condition that can not be met easily with preneoplasia and early neoplasia. Molecular demonstration of a genetic lesion, as small as a point mutation, within all cells is evidence that a common stem cell contributed that mutation This approach applies only to that fraction of cases in which a "marker" mutation can be identified and specifically fails to identify clonal proliferation that might take place prior lo creation of a specific genetic lesion*
Currently, successful molecular clonality assays are based upon analyses of widely-dispersed hypcrvariable regions of the human genome, composed of repetitive DNA sequences Microsalellites have assumed an increasingly important role in this task due to their ubiquity. PCR (polymerase chain reaction) typability, Mendelian co-dominant inheritance, and extreme polymorphism.
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