These findings are broadly consistent with an earlier interpretation of primary breast cancer FACS/SKY profiles 46, and has recently been recapitulated in studies of macro-dissected and ploidy-sorted cell populations 14, and single cell sequencing15 of primary breast tumors. We note that this model represents a departure from the idea that tetraploidization is an initiating event 47,13,26,48,49. In addition, the association of genome lineage (Fig. 6c) and with age at diagnosis in ovarian carcinoma (Fig. 7d) is consistent with a recently described mechanism linking telomere crisis, DNA damage response, and genome doubling in cultured mouse embryonic fibroblasts 48.
