From the Labs: Biomedicine

Better Cancer Tracking
Physicians could monitor cancer by screening for tumor DNA

Source: “Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing”
Victor Velculescu et al.
Science Translational Medicine 2: 20ra14

Results: Researchers from Johns Hopkins University analyzed the DNA of tumors in patients with breast and bowel cancer and found regions of abnormal, re­arranged DNA that served as unique biomarkers of each patient’s disease. They then measured levels of cancer-specific DNA in one patient before and after treatment. The ratio of cancer DNA to normal DNA in blood samples dropped dramatically after treatment, but the marker was still detectable, suggesting that the patient should be monitored more closely for possible recurrence of the disease.

Why it matters: Cancer arises when a number of genetic alterations in cells allow them to grow uncontrollably. Tracking those alterations in a patient’s cancer DNA could provide a new way of detecting small tumors or stray cancer cells that linger after treatment. Scientists say the DNA changes detected in the study will prove much more accurate than existing biomarkers such as the prostate-specific antigen (PSA) associated with prostate cancer, which may yield false positives because even healthy cells can produce the protein.

Methods: Researchers compared the genome sequence of patients’ healthy DNA and DNA isolated from tumor tissue. After isolating unique tumor signatures, they developed a test that uses DNA amplification to measure the amount of tumor DNA and normal DNA in blood.

Next steps: To determine how the technology can be most useful in medicine, researchers will use it to analyze different tumor types as well as different stages of tumor progression. They are also working on automating the technique and reducing its cost.

Source: “Direct conversion of fibroblasts to functional neurons by defined factors”
Marius Wernig et al.
Nature 463: 1035-1041

Results: By making a few simple genetic tweaks, scientists can transform mouse skin cells directly into brain cells, without first returning them to the embryonic state required by previous methods. The resulting cells express neuron-specific genes, have the characteristic branching shape of neurons, and form connections both with each other and with regular neurons collected from the brain.

Why it matters: The research could someday offer an effective way to replace damaged neurons. Because brain cells derived from a skin graft would be genetically identical to the patient’s own tissue, they wouldn’t carry the risk of immune rejection associated with transplants. And scientists say the technique is faster than the existing approach to generating replacement brain cells from an individual patient: reprogramming adult cells to behave like embryonic cells and then prodding them to develop into neurons.

Methods: Scientists began by studying the genes for 19 transcription factors–proteins that bind to DNA and regulate expression of other genes. All were known to play a role in neural development and were found only in the brain. When the researchers used viruses to deliver two genes known to be particularly important for neural development into skin cells growing in a dish, they discovered that one of them had the power to convert the cells into what looked like immature neurons. They identified two additional genes that made the process faster and more consistent.

Next steps: The researchers are trying to repeat the process with human cells. They also plan to transplant the reprogrammed mouse cells into the brains of engineered mice that have a disease similar to Parkinson’s. Those experiments could reveal whether the cells can function properly in the brain and relieve symptoms of the disease.