Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype

摘要: Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of cancer stem cell hypothesis. To investigate this issue, we performed combined analyses markers associated with cellular differentiation states genotypic alterations in human breast carcinomas evaluated diversity ecological evolutionary methods. Our showed high degree both within between distinct populations that were defined based on phenotypes including cell-like characteristics. In several tumors, more-differentiated genetically distinct, leading us to question validity simple hierarchy-based model. correlated clinically relevant subtypes some tumors was markedly different situ invasive populations. We also found measures clinical variables. findings highlight importance value analyzing as cells more effectively plan treatments.