U-M researchers take step toward bringing precision medicine to all cancer patients
New assay simplifies gene sequencing analysis
ANN ARBOR, Mich. — Doctors at the University of Michigan Rogel Cancer Center envision analyzing the genetic make-up of every cancer patient’s tumor to determine the best treatment course for that patient.
They’re already part of the way there: A gene sequencing program called Mi-ONCOSEQ scans the DNA and RNA of patients with advanced cancer. A team of precision medicine experts then meets to help align the findings with potential treatments or clinical trials.
Now, working with Thermo Fisher Scientific, researchers have developed and tested a new tool that may take it to the next level.
“We have a lot of experience at the University of Michigan in figuring out how to apply personalized medicine to patients with cancer. One of the main challenges we’ve found is that doing the analysis is a major bottleneck. Our goal was to find a way to make the process easier to scale to a larger volume of patients so that we can do this for all our patients,” says Scott A. Tomlins, M.D., Ph.D., assistant professor of pathology and urology at the University of Michigan Medical School.
Tomlins is the senior author on a paper published in Neoplasiathat describes the new tool, called the Oncomine Comprehensive Panel.
The researchers sifted through a database of more than 700,000 tumor samples and identified the most common genetic variants across cancer types. They then filtered the list to include those variants associated with FDA-approved drugs, referenced in clinical guidelines, or associated with investigational therapies in clinical trials.
The researchers evaluated the panel on more than 300 tissue samples, including more than 100 that had also been tested by routine clinical genomic testing. The assay confirmed the previously identified genetic changes. It also identified additional relevant variants in the tissue samples.
The new assay completes sequencing more quickly and for less money than current sequencing platforms. It also can be used with a large range of tumor sample types, including small biopsies and archived tissue samples. In the future, this may mean that patients would not always need to undergo a fresh biopsy in order to identify a potential treatment strategy, as is currently necessary with more comprehensive sequencing approaches.
“One of the real challenges of personalized medicine is the idea that we’re going to find a truly actionable target for every patient. What we’re finding is that’s not always the case, particularly when we look at samples from patients who have failed multiple lines of standard therapy,” Tomlins says. “The future of personalized medicine will mean knowing early in the disease course what genetic variant drives a patient’s tumor. Then we would be able to put them on the best treatment path as soon as possible.
“The result of this study is that we can now help clinical researchers overcome challenges that had prevented the routine use of next-generation sequencing to identify and prioritize relevant gene variants,” said study co-author Dan Rhodes, Ph.D., vice president of oncology strategy at Thermo Fisher Scientific. “As we have demonstrated, it is now possible to apply a highly scalable, targeted sequencing approach to detect relevant cancer variants, opening the door for routine clinical applications in the near future.”
Patients interested in learning more about genetic sequencing opportunities or clinical trials at the University of Michigan can call the U-M Cancer AnswerLine at 800-865-1125.
Additional authors: From U-M: Daniel H. Hovelson, Andrew S. McDaniel, Andi K. Cani, Venkata Yadati, Anmol Amin, Javed Siddiqui, Bryan L. Betz, Kathleen A. Cooney, Felix Y. Feng, Michael H. Roh, Chia-Jen Liu, David G. Beer, Arul M. Chinnaiyan, Daniel R. Rhodes. From Thermo Fisher Scientific: Bryan Johnson, Kate Rhodes, Paul D. Williams, Santhoshi Bandla, Geoffrey Bien, Paul Choppa, Fiona Hyland, Rajesh Gottimukkala, Guoying Liu, Manimozhi Manivannan, Jeoffrey Schageman, Efren Ballesteros-Vallagrana, Peter Wyngaard, Seth Sadis. From Oregon Health & Sciences University: Catherine S. Grasso, Michael J. Quist. From Thomas Jefferson University: Karen E. Knudsen. From Fred Hutchinson Cancer Research Center: Peter S. Nelson.
Funding: Evans Foundation/Prostate Cancer Research Foundation; National Institutes of Health grants R01 CA183857, R01 CA181605, R01 CA 159945, R01 CA154365, UM1 HG006508; U.S. Department of Defense; Life Technologies/Thermo Fisher Scientific; Stand Up to Cancer-Prostate Cancer Foundation; A. Alfred Taubman Medical Research Institute
Disclosure: The University of Michigan has been issued a patent on the detection of ETS gene fusions in prostate cancer, on which Chinnaiyan and Tomlins are listed as co-inventors. The University of Michigan licensed the diagnostic field of use to Gen-Probe Inc., who has sublicensed some rights to Ventana/Roche. Tomlins serves as a consultant to and has received honoraria from Ventana/Roche. Tomlins has a sponsored research agreement with Thermo Fisher Scientific, which supported this work
Reference: Neoplasia, Vol. 17, No. 4, pp. 385-399, doi:10.1016/j.neo.2015.03.004