From the Labs: Biomedicine

Cancer Genome
Comparing healthy cells and cancer cells reveals genetic missteps in cancer

Source: “DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome”
Elaine Mardis et al.
Nature 456: 66-72

Results: Scientists from Washington University in St. Louis identified 10 genetic mutations found in the DNA of cancer cells but not in healthy cells. Both sets of cells were collected from a patient who had leukemia.

Why it matters: Previous studies that analyzed tumor DNA focused on genes thought to play a role in cancer, thus neglecting much of the genome. The new study provides an unbiased search through the entire genome, identifying genetic variants that scientists might never have noticed. The findings provide new targets for further research and drug development.

Methods: The scientists used a new sequencing tech­nology, from San Diego-based ­Illumina, that is much cheaper than traditional methods. For the first time, they created full-genome sequences of both cancerous and healthy cells taken from the same person, a woman who died of acute myelogenous leukemia. By comparing the two sequences, they identified specific changes found only in the cancer cells.

Next steps: The scientists have almost finished sequencing the genome of a second patient. Because this patient is still alive and in remission, the genetic variants identified in his cancer cells may reveal clues to what makes treatment successful. The researchers are also planning to sequence genomes from different types of solid tumors.

Source: “Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway”
Zhigang He et al.
Science 322: 963-966

Results: Mice with two deleted genes recovered from optic-nerve injury better than normal mice did. Up to 50 percent of their neurons survived two weeks after injury, versus about 20 percent in the control mice. Axons–the long projections in neurons that transmit signals from one cell to another–showed significant regrowth in about 10 percent of the genetically modified animals, but none in the controls.

Why it matters: Nerve cells don’t normally regenerate in adults after injury, so new methods to boost their growth could spur recovery. Other research has demonstrated axon regrowth, but the magnitude of growth in this study makes it significant: some axons grew up to four millimeters in a month. Chemical inhibitors of one of the deleted genes already exist, raising the possibility that the same approach could be applied to humans.

Methods: The researchers deleted two genes, known as Pten and Tsc1, that normally inhibit neural cell growth in the brains of mice. They then crushed the optic nerve. Two weeks after the injury, the scientists tagged the crushed cells with fluorescent markers to assess cell growth and survival.

Next steps: The research group is testing the effect of deleting the same genes in mice with spinal-cord injuries. They are also developing small-molecule compounds that could mimic the deletion of Pten or Tsc1 to boost axon regeneration and functional recovery in patients.