Researchers from Huntsman Cancer Institute (HCI) at the University of Utah report they have discovered a method to identify cancer-causing rearrangements of genetic material called chromosomal translocations quickly, accurately, and inexpensively. A description of the method and the research results appear online in this month's issue of the EMBO Molecular Medicine journal.
Many cancers result from chromosomal translocations in tumor cells. Hundreds of cancer-causing translocations have been discovered, but current methods for detecting them have significant shortcomings.
The technique, developed in the lab of Stephen Lessnick, M.D., Ph.D., director of the Center for Children's Cancer Research at HCI, combines microarray technology, which can look for thousands of translocations in a single test, with a novel antibody that is used to detect the presence of the translocation . "We're moving past the age when a pathologist looking through the microscope at a tumor sample is the best way to diagnose what type of cancer it is," said Lessnick. "The molecular tests currently available are slow, inefficient, and expensive, and one of the biggest issues is that you need high-quality tumor samples, not always available in the clinical setting, to do them." According to Lessnick, his method tolerates real-life specimens much better than the current standard techniques.
"Originally, this method was used in HCI's Cairns lab (headed by Bradley R. Cairns, Ph.D.) to study RNA in yeast. We took their method and applied it to our study of chromosomal translocations in human tissue," Lessnick said. He said the next task is to find a commercial partner to develop this research from a 'proof of principle' into a diagnostic test that doctors can use to help their patients.
"With this method, there's potential to develop a single array that could test for every known cancer-causing translocation simultaneously. Currently, a clinician has to decide beforehand which specific cancer to test," he said.
The research used Ewing's sarcoma (a rare childhood cancer) as the case study for developing the method, but Lessnick maintains that the technology can be easily applied to any type of cancer caused by a translocation.
Funding for this project came from the National Institutes of Health's Innovative Molecular Analysis Technology program. The program focuses on rapid movement of new ideas from basic science labs (such as the Cairns lab) out into the clinical realm. "They were willing to fund this idea without a lot of preliminary data because it showed good potential to move toward clinical uses," said Lessnick.
Lessnick is a Jon and Karen Huntsman Presidential Professor in Cancer Research, and a professor in the Division of Pediatric Hematology/Oncology at the University of Utah. Other HCI investigators participating in the research include Bradley R. Cairns, Ph.D., HCI Senior Director of Basic Science, Howard Hughes Medical Institute Investigator, and professor in the Department of Oncological Sciences at the University of Utah, as well as Brett Milash, Ph.D., and Brian Dalley, Ph.D., of the Microarray and Genomic Analysis Core Facility.
This work was supported by the NIH via R21 CA138295 to SLL, T32 GM007464 to ND, and P30 CA042014 to Huntsman Cancer Institute. Cairns is supported by the Howard Hughes Medical Institute. Additional work in the Lessnick lab is supported by Sidney's Incredible Defeat of Ewing's Sarcoma (SIDES).
- Wen Luo, Brett Milash, Brian Dalley, Richard Smith, Holly Zhou, Natalie Dutrow, Bradley R. Cairns, Stephen L. Lessnick. Antibody detection of translocations in Ewing sarcoma. EMBO Molecular Medicine, 2012; DOI: 10.1002/emmm.201200225
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