According to the present view, @entity3 marks the end in a sequence of genomic changes underlying the progression of an epithelial cell to a lethal @entity5 . Here, we aimed to find out at what stage of @entity5 development transformed cells leave the @entity5 and whether a defined genotype corresponds to @entity3 . To this end, we isolated single disseminated @entity5 cells from bone marrow of @entity0 @entity1 and performed single-cell comparative genomic hybridization. We analyzed disseminated @entity5 cells from @entity1 after curative resection of the @entity5 (stage M0), as presumptive progenitors of manifest @entity3 , and from @entity1 with manifest @entity3 (stage M1). Their genomic data were compared with those from microdissected areas of matched @entity5 . Disseminated cells from M0-stage @entity1 displayed significantly fewer @entity5 or cells from M1-stage @entity1 (P < 0.008 and P < 0.0001, respectively), and their aberrations appeared to be randomly generated. In contrast, @entity5 and M1 cells harbored different and characteristic chromosomal imbalances. Moreover, applying machine-learning methods for the classification of the genotypes, we could correctly identify the presence or absence of @entity3 in a @entity1 on the basis of a single-cell genome. We suggest that in @entity0 , @entity5 cells may disseminate in a far less progressed genomic state than previously thought, and that they acquire genomic aberrations typical of metastatic cells thereafter. Thus, our data challenge the widely held view that the precursors of @entity3 are derived from the most advanced clone within the @entity5 .

From latent disseminated cells to overt @entity3 : genetic analysis of systemic XXXX progression.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'primary tumors', 'chromosomal aberrations than primary tumors', 'cancer', 'primary tumor'] @entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis', 'metastatic disease']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
