title: Characterization of human embryonic stem cells with features of neoplastic progression.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tamra E
authors.initials: TE
authors.lastname: Werbowetski-Ogilvie
authors.forename: Marc
authors.initials: M
authors.lastname: Bossé
authors.forename: Morag
authors.initials: M
authors.lastname: Stewart
authors.forename: Angelique
authors.initials: A
authors.lastname: Schnerch
authors.forename: Veronica
authors.initials: V
authors.lastname: Ramos-Mejia
authors.forename: Anne
authors.initials: A
authors.lastname: Rouleau
authors.forename: Tracy
authors.initials: T
authors.lastname: Wynder
authors.forename: Mary-Jo
authors.initials: MJ
authors.lastname: Smith
authors.forename: Steve
authors.initials: S
authors.lastname: Dingwall
authors.forename: Tim
authors.initials: T
authors.lastname: Carter
authors.forename: Christopher
authors.initials: C
authors.lastname: Williams
authors.forename: Charles
authors.initials: C
authors.lastname: Harris
authors.forename: Joanna
authors.initials: J
authors.lastname: Dolling
authors.forename: Christopher
authors.initials: C
authors.lastname: Wynder
authors.forename: Doug
authors.initials: D
authors.lastname: Boreham
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D003582:Cytogenetics; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005821:Genetic Techniques; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism
chemical_list: D016222:Fibroblast Growth Factor 2