Letter abstract
Nature Biotechnology 27, 91 - 97 (2009)
Published online: 4 January 2009 | doi:10.1038/nbt.1516
Characterization of human embryonic stem cells with features of neoplastic progression
Tamra E Werbowetski-Ogilvie1, Marc Bossé1, Morag Stewart1, Angelique Schnerch1, Veronica Ramos-Mejia1, Anne Rouleau1, Tracy Wynder1, Mary-Jo Smith2, Steve Dingwall3, Tim Carter3, Christopher Williams4, Charles Harris4, Joanna Dolling5, Christopher Wynder1, Doug Boreham3 & Mickie Bhatia1
Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced 'stemness'. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor-initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization reveals an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells.
- Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, MDCL 5029, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
- Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
- Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
- PerkinElmer Life and Analytical Sciences, 940 Winter Street, Waltham, Masschusetts 02451, USA.
- Department of Pathology and Molecular Medicine, Credit Valley Hospital, 2200 Eglinton Avenue West, Mississauga, Ontario L5M 2N1, Canada.
Correspondence to: Mickie Bhatia1 e-mail: mbhatia@mcmaster.ca
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