Cancer-Causing DNA Found In Some Stem Cells Used In Patients.
Published in the April 2017 issue of Nature, the International Weekly Journal of Science, Kevin Eggan and Steven McCarroll and their colleagues from Harvard University (Cambridge), King’s College (London) and the Hebrew University of Jerusalem (Jerusalem), raised the alarm that certain cancer-causing DNA were found in some stem cells that had been used in patients. Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. Researchers sequenced the protein-coding genes of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use. They then applied computational strategies for identifying mutations present in a subset of cells in each hES cell line. Although such mosaic mutations were generally rare, they identified five unrelated hES cell lines that carried six mutations in the TP53 gene that encodes the tumour suppressor P53. The TP53 mutations observed were dominant negative and were the mutations most commonly seen in human cancers. As the acquisition and expansion of cancer-associated mutations in hPS cells may go unnoticed during most applications, the researchers suggested that careful genetic characterisation of hPS cells and their differentiated derivatives be carried out before clinical use. This may just be the tip of the iceberg, as what other mutations are extant and yet to be discovered in certain stem cell lines.
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