By: Kseniya Golovnina, PhD
RNA-Seq Technology for Oncotargets Discovery
One of the most significant discoveries in cancer research, using the “Big Data” approach with experimental validations, was made recently by Chinese and American scientists together with Splicingcodes.com. They described the first cancer predisposition, familially-inherited, fusion gene, KANSARL, specific to populations with European ancestry, by using advanced RNA-sequencing (RNA-seq) of cancer transcriptomes.
A fusion gene is a hybrid formed from two previously separate genes as a result of chromosomal rearrangements. Often, fusion genes are oncogenes. The first fusion gene abnormality was described in a human malignancy and was called the Philadelphia chromosome. In the early 1980s, scientists showed that a translocation between chromosomes 9 and 22 led to the formation of a fusion gene (BCR/ABL1), which produced a chimeric protein with the capacity to induce chronic myeloid leukemia. KANSARL is the most prevalent cancer gene discovered so far. Scientists systematically analyzed the RNA-seq data of many cancer types from different parts of the world, together with RNA-seq datasets of the 1000 Genome Project. KANSARL fusion transcripts were rarely detected in tumor samples of patients from Asia or Africa, but occurred specifically in 28.9% of the population of European origin.
Scientists from Cancer Genome Anatomy project at the National Cancer Institute (NCI), using sophisticated sequencing techniques, have identified 10,676 gene fusions among cancer-related chromosomal aberrations. Splicingcodes.com has identified over 1.1 million novel fusion transcripts, many of which are likely biomarkers of diseases. Fusion genes play an important role in diagnosis and monitoring of cancer treatment progress by measuring the disappearance of the fusion and, thereby, the disappearance of the tumor tissue. Currently, several clinical trials are aimed at treating fusion-positive patients with a range of targeted therapies, which will hopefully lead to novel therapy development and save patients’ lives. (Splicingcodes)
Turning Mammalian Cells into Biocomputers to Treat Human Disease
Engineering cells by manipulating DNA and controlling their performance is a growing field of synthetic biology. Scientists have been working with bacterial cells for years to perform different controlled actions, for example, lighting up when oxygen levels drops. Bacterial cells, including Escherichia coli, have a simple genome structure and are relatively easy to manipulate. Using bacterial cells, it was possible also to join several genetic circuits within a single cell to carry out more complex actions.
After successful engineering in bacteria, researchers have aimed to create genetic circuitry to detect and treat human disease in mammalian cells. Most of the attempts have failed due to the complexity of the mammalian genome, until a group of biomedical engineers from Boston and Basel, Switzerland decided to upgrade their DNA “switches”. They used an ability of special enzymes, DNA recombinases, to selectively cut and stitch DNA. The new system in mammalian cells is called ‘Boolean logic and arithmetic through DNA excision’ (BLADE). BLADE founders built a wide variety of circuits (113), each designed to carry out a different logical operation with 96.5% success. This Boolean system has great potential for applications in cell and tissue engineering. One exciting possibility is engineering T-cells with genetic circuits that initiate a suicide response to kill tumors when they detect the presence of two or three “biomarkers” produced by cancer cells. (Robert F. Service, ScienceNews)
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