Gene fusion shifts cell activity into high gear, causing some cancer

ScienceDaily | 1/3/2018 | Staff
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The study was published online today in the journal Nature.

In a 2012 study published in Science, the CUMC team found that some cases of glioblastoma, the most common and aggressive form of primary brain cancer, are caused by the fusion of two genes, FGFR3 and TACC3. At the time, it was thought that this gene fusion was limited to a fraction of brain tumors, affecting about 300 patients in the U.S. per year.

Researchers - Gene - Fusion - Percentage - Lung

Since then, however, other researchers have observed the same gene fusion in a percentage of lung, esophageal, breast, head and neck, cervical, and bladder cancers, affecting tens of thousands of cancer patients overall. "It's probably the single most common gene fusion in human cancer," said study co-leader Antonio Iavarone, MD, professor of neurology and of pathology and cell biology (in the Institute for Cancer Genetics) at CUMC. "We wanted to determine how FGFR3-TACC3 fusion induces and maintains cancer so that we could identify novel targets for drug therapy."

Changes in mitochondria -- the 'powerhouse' of the cell -- have been observed in cancer for a long time, but researchers have found only recently that mitochondrial activity and cellular metabolism are linked to certain cancers. However, the mechanism by which genetic mutations alter mitochondrial activity and promote tumor growth was unknown.

Study - CUMC - Researchers - Activity - Thousands

In the current study, the CUMC researchers compared the activity of thousands of genes in cancer cells with and without FGFR3-TACC3. They discovered that the fusion greatly increases the number and accelerates the activity of mitochondria. Cancer cells, which require huge amounts of energy to rapidly divide and grow, can thrive when mitochondrial activity has been amped up.

Using a variety of experimental techniques, the researchers determined that the gene fusion initiates a cascade of events that increases mitochondrial activity. First, FGFR3-TACC3 activates a protein called PIN4. Once activated, PIN4 travels...
(Excerpt) Read more at: ScienceDaily
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