It may be that genetically abnormal embryos do not form hESC lines as easily as normal ones. It is unlikely that the abnormalities in CH-ES1 would have been caused by the derivation process itself or by early culture, because we used identical conditions to those used to produce the 30 chromosomally normal hESC lines, who succeeded in deriving hESC lines from embryos that were established for the study of early development, obtained a cytogenetically abnormal line. There are several possible explanations for the malignancy of the CH-ES1 and the teratocarcinoma lines, including partial triploidy. Many of the trisomies that have been identified in cancers and culture-adapted cells were also seen in CHES1 cells, such as trisomy of chromosomes a duplication. In Ixabepilone addition, there were trisomies of chromosomes 9, 19, 20 and 21. In fact, only chromosome 14 was normal in the CGH assays of the CH-ES1 line. It is not difficult to understand why this particular cell line is particularly malignant and invasive. According to the CGH analysis, the Obatoclax changes observed in H1 may have been there from the beginning. However, it is also possible that these changes arose during culture adaptation. We do not presently have CGH or SNP array data from earlier passages or from other laboratories. Culture adaptation of hESCs and accumulation of chromosomal changes during long term culture occur as a result of the successive increase of selective growth advantages provided by certain abnormalities in the cells. Furthermore, smaller changes than can be seen by G-banding have been described, and these may offer growth advantages similar to those that occur in cancer. Impaired imprinting and aberrations in mitochondrial DNA have been described, and impaired X-chromosome activation occurs during culture adaptation. Culture adaptation has also been described in teratocarcinoma lines. It is possible that least some of the aberrations in the studied lines are caused by culture adaptation. The aneuploidic increases in copy number of genes that may promote tumor formation, including ARHGAP26, GRB10, DDHD2, FGFR1, CTNNA3, PTPN1 and MLLT1 in the apparently stable and karyotypically normal lines HS293 and HS401, are cause for concern.