Does HUMARA assay for assessment of clonal hematopoiesis have shortcomings?

摘要

Determination of clonality based on assays of inactivation of genes encoded on the X chromosome has provided important insights into the origins of neoplastic diseases. The following characteristics make a clonality assay informative: (1) the gene being assayed must undergo X inactivation such that only one allele is expressed in a somatic cell in females; (2) the gene of interest should be sufficiently polymorphic so as to be informative in a reasonably high proportion of the population; (3) the assay should be quantitative because skewing of X inactivation is a normal biologic process determined by the proportion of cells with an active paternal or maternal X chromosome that occurs randomly during embryogenesis; and (4) the assay should be sufficiently robust so that accurate determinations applicable to a variety of tissues can be made at various X chromosome loci.1 The human androgen receptor gene (HUMARA) assay has been widely used to establish clonality; however, we and others had concerns that the assay might produce spurious results.