A teratocarcinoma-like human embryonic stem cell (hESC) line and four hESC lines reveal potentially oncogenic genomic changes - PubMed (original) (raw)

. 2010 Apr 23;5(4):e10263.

doi: 10.1371/journal.pone.0010263.

Marisa Jaconi, Virpi Töhönen, Frédérique Béna, Stefania Gimelli, Alexis Bosman, Frida Holm, Stefan Wyder, Evgeny M Zdobnov, Olivier Irion, Peter W Andrews, Stylianos E Antonarakis, Marco Zucchelli, Juha Kere, Anis Feki

Affiliations

A teratocarcinoma-like human embryonic stem cell (hESC) line and four hESC lines reveal potentially oncogenic genomic changes

Outi Hovatta et al. PLoS One. 2010.

Abstract

The first Swiss human embryonic stem cell (hESC) line, CH-ES1, has shown features of a malignant cell line. It originated from the only single blastomere that survived cryopreservation of an embryo, and it more closely resembles teratocarcinoma lines than other hESC lines with respect to its abnormal karyotype and its formation of invasive tumors when injected into SCID mice. The aim of this study was to characterize the molecular basis of the oncogenicity of CH-ES1 cells, we looked for abnormal chromosomal copy number (by array Comparative Genomic Hybridization, aCGH) and single nucleotide polymorphisms (SNPs). To see how unique these changes were, we compared these results to data collected from the 2102Ep teratocarcinoma line and four hESC lines (H1, HS293, HS401 and SIVF-02) which displayed normal G-banding result. We identified genomic gains and losses in CH-ES1, including gains in areas containing several oncogenes. These features are similar to those observed in teratocarcinomas, and this explains the high malignancy. The CH-ES1 line was trisomic for chromosomes 1, 9, 12, 17, 19, 20 and X. Also the karyotypically (based on G-banding) normal hESC lines were also found to have several genomic changes that involved genes with known roles in cancer. The largest changes were found in the H1 line at passage number 56, when large 5 Mb duplications in chromosomes 1q32.2 and 22q12.2 were detected, but the losses and gains were seen already at passage 22. These changes found in the other lines highlight the importance of assessing the acquisition of genetic changes by hESCs before their use in regenerative medicine applications. They also point to the possibility that the acquisition of genetic changes by ESCs in culture may be used to explore certain aspects of the mechanisms regulating oncogenesis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Cartography of genetic aberrations which were found in the CH-ES1 and, 2102Ep cell lines.

A) Line CH-ES1, B) Line 2102Ep. Blue bars show duplicated regions and red ones show deleted regions.

Figure 2

Figure 2. The number of genes in CH-ES1, 2102Ep and H1 lines in either deleted or duplicated regions.

A) deleted regions, B) duplicated regions.

Figure 3

Figure 3. The number of aberrations per cell line detected by Affymetrix SNP6.0 arrays.

Figure 4

Figure 4. Pathway analyses of gained and lost genes in the analysed cell lines.

A) The number of pathways which were statistically significantly enriched per line involving deleted (left panel) and duplicated (right panel) genes. B) The number of lost and gained genes per cell line in summary pathways. C) The percentage of genes altered per pathway by deletion or duplication. Only pathways with copy number variations are shown.

Figure 5

Figure 5. The number of CNVs and UPDs per chromosome and cell line as detected by Affymetrix 6.0 arrays.

CH-ES1 and 2102Ep are the only female lines. A) The numer of CNVs, B) The number of UPDs.

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