MUSC dean helps show how data can catalyze precision medicine

The first analysis of nearly 19,000 de-identified genomic records from the American Association for Cancer Research international data-sharing initiative known as AACR Project Genomics Evidence Neoplasia Information Exchange, or GENIE, has been published in the journal Cancer Discovery. 

The dean of the College of Medicine at the Medical University of South Carolina, Raymond DuBois, M.D., Ph.D., had an integral role on the team working on that initiative for more than two years. He said the project is remarkable in that it provides for the collection, curation and sharing of large data sets from multiple institutions. “This dramatically increases the power of these studies and will ultimately allow for this data to be accessed and studied widely," DuBois said.

DuBois is past president of AACR and the current president/chairman of the AACR Foundation Board. He helped secure funding for the project from the AACR, oversaw GENIE project development as a member of the oversight committee and was one of the presenters of the results of project GENIE at the 2017 AACR meeting in Washington, D.C.

In addition to the genomic analysis, the report includes examples of how the AACR Project GENIE genomic data can be used to facilitate clinical research, including:

• Analysis showing that more than 30 percent of the samples had mutations that are clinically actionable, meaning that they are suggestive of a specific treatment that is either already approved by the U.S. Food and Drug Administration or is being tested in clinical trials. 
• Analysis showing that the rate at which patients with samples in the AACR Project GENIE registry would match with arms of the NCI-MATCH trial reflected the actual accrual rates for the trial.
• Details of two additional studies underway that are linking certain genetic characteristics of metastatic breast cancer with clinical and pathological features of the tumors, as well as with patient outcomes.

Charles L. Sawyers, MD, FAACR, is the AACR Project GENIE Steering Committee chairman and an author on the paper. “There has been a lot of discussion about the potential of data-sharing initiatives to accelerate the pace of progress against cancer. This paper shows that AACR Project GENIE has made the first steps to delivering on this promise,” Sawyers said.

“We are particularly excited by the clinical actionability analysis,” continued Sawyers, who is also chairman of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center in New York, and a Howard Hughes Medical Institute investigator. “Prior studies looking at how often tumor genome sequencing identifies a clinically actionable mutation have yielded variable results, leading some to question its clinical utility. The huge number of samples in our study and the high rate of clinical actionability give us confidence that tumor genome sequencing can have an important role in clinical care.”

AACR Project GENIE is a multi-phase, multi-year, international data-sharing project that was launched by the AACR in partnership with eight global academic leaders in clinical cancer genomics in November 2015. Just over a year later, in January 2017, the AACR Project GENIE consortium made public nearly 19,000 de-identified genomic records collected from patients who were treated at the eight international institutions participating in the first phase of the project.

Ethan Cerami, Ph.D., directs the Knowledge Systems Group and lead scientist in the Department of Biostatistics and Computational Biology at the Dana-Farber Cancer Institute in Boston and is an author on the paper “This paper describes the AACR Project GENIE consortium and provides a landscape overview of the first public GENIE data release,” he said. “By showing that we can share data across multiple institutions in the United States, Canada, and Europe to obtain results none of the institutions could have obtained alone, we have put AACR Project GENIE at the forefront of data-sharing efforts to accelerate scientific discovery and ultimately improve patient care.”

The paper provides detailed information about the data collected at the different institutions, highlighting that even though the types of sequencing and size of the gene panels used at the individual institutions differ and are evolving over time, the data can be compared across institutions. The high-level analysis of the nearly 19,000 de-identified genomic records made public by the consortium also shows many similarities with the data in The Cancer Genome Atlas, or TCGA. The paper also highlights several differences with TCGA data, which the authors speculate are a result of a greater proportion of the AACR Project GENIE records coming from patients with recurrent or relapsing disease.

The eight institutions that participated in AACR Project GENIE phase 1 are: Dana-Farber Cancer Institute, Boston; Gustave Roussy Cancer Campus, Paris-Villejuif, France; The Netherlands Cancer Institute, Amsterdam, on behalf of the Center for Personalized Cancer Treatment, Utrecht, The Netherlands; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore; Memorial Sloan Kettering Cancer Center, New York; Princess Margaret Cancer Centre, Toronto; University of Texas MD Anderson Cancer Center, Houston; and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

This study was supported by funds from the AACR, Genentech, Boehringer Ingelheim, Pfizer, Eli Lilly, the Howard Hughes Medical Institute, the National Institutes of Health, the National Cancer Institute, the Princess Margaret Cancer Foundation, the Ontario Ministry of Health, Susan G. Komen, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the T.J. Martell Foundation, the Commonwealth Foundation, the Cancer Prevention & Research Institute of Texas, the Dutch Ministry of Health, and the Dutch Cancer Society. Sawyers serves on the Board of Directors of Novartis. Cerami declares no conflicts.

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Most content for this report was created by the American Association for Cancer Research.