[November 22, 2017]

Analysis of Large-Scale Multiple Myeloma Data by USC Translational Genomics Scientists Reveals Mutation Differences Between African American and Caucasian Patients

Researchers from the Keck School of Medicine of the University of Southern California (USC) Department of Translational Genomics and collaborating institutions who analyzed an unprecedented large-scale collection of publicly available data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study found that Caucasian patients' cancers are more likely to have mutations associated with a worse prognosis. This may suggest that poorer health outcomes for African American patients are linked more to socioeconomic status and limited access to quality medical care, rather than to cancer biology. The study also identified new cancer gene mutations that are significantly more prevalent in African Americans, linking these genes to multiple myeloma for the first time and strongly supporting the need for diverse cohorts to better understand the role of population heterogeneity in cancer. The findings were published today in PLoS Genetics.

Multiple myeloma is a form of blood cancer that affects plasma cells, an important component of the immune system found in bone marrow. The American Cancer Society estimates that 30,000 new cases of multiple myeloma will be diagnosed in the U.S. this year, and that nearly 13,000 patients will die from it. African American patients are three times more likely to be diagnosed with this type of cancer and twice as likely to die from it than Caucasians of the same age and gender. In the past decade, new treatments for the disease have spurred a remarkable improvement in survival for myeloma patients, but those benefits have disproportionately increased survival rates for affected Caucasian patients.

"One of the most surprising discoveries from this large cohort is that cancers from patients of European descent were six times more likely than their African-descent counterparts to have mutations in TP53, a known tumor suppressor gene," said Zarko Manojlovic, PhD, Assistant Professor of Research in the Department of Translational Genomics and lead author of the paper. "Biologically speaking, higher mutation rates in this gene should lead to overall lower survival rates among patients of European descent, but that does not correlate with what we see in clinical outcomes. Going forward, we hope to functionally validate these results for more insight into the underlying biology."

This study represents the largest comprehensive molecular analysis of racially and ancestrally defined, newly diagnosed multiple myeloma patients and one of the largest diverse cancer cohort studies to date, including a significant number of African American patients. The scientists analyzed publicly available whole exome, transcriptome, and clinical data from 718 multiple myeloma patients participating in the MMRF CoMMpass Study. They used genetic analysis to determine ancestry for all patients. The population ultimately included 127 patients of African descent and 591 patients of European descent, making it one of the largest cancer genomics studies performed to date.

"We in the cancer genomics community have a responsibility to ensure that our studies represent true population diversity so we can understand the role of ancestry and biology in health outcomes," said John D. Carpten, PhD, Chair of the Department of Translational Genomics at the Keck School of Medicine and senior author of the paper. "The new candidate myeloma genes we identified in the African American population may have been overlooked because of the lack of diversity in previous genomic efforts. There are clearly molecular differences between African American and Caucasian multiple myeloma cases, and it will be critical to purse these observations to better improve clinical management of the disease for all patients."

Daniel Auclair, PhD, Senior Vice President of Research at the Multiple Myeloma Research Foundation and co-author of the paper, commented: "The CoMMpass Study is part of our commitment to extending the lives and accelerating precision medicine for every patient living with Multiple Myeloma. These results are gratifying as they provide clinically actionable results for patients."

Jonathan Keats director of Bioinformatics at the Translational Genomics Research Institute in Arizona and a co-author of the study, added, "This study provides a unique view on the genetic differences of multiple myeloma in African-American and Caucasian populations that is only possible in studies like the Multiple Myeloma Research Foundation CoMMpass Study, which was designed to collect a patient cohort reflective of the demographics of the United States population."

To learn more about the USC Department of Translational Genomics, visit dtg.usc.edu.

Paper cited: Zarko Manojlovic et al. Comprehensive molecular profiling of 718 Multiple Myelomas Reveals Significant Differences in Mutation Frequencies Between African and European Descent Cases. PLoS Genetics.

ABOUT THE KECK SCHOOL OF MEDICINE OF USC

Founded in 1885, the Keck School of Medicine of USC is among the nation's leaders in innovative patient care, scientific discovery, education and community service. It is part of Keck Medicine of USC, the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes the Keck Medical Center of USC, composed of the Keck Hospital of USC and the USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school has approximately 1,650 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 800 medical students and 1,000 students pursuing graduate and postgraduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school's faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals Children's Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the USC Norris Comprehensive Cancer Center, the Zilkha Neurogenetic Institute, the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, the USC Cardiovascular Thoracic Institute, the USC Roski Eye Institute and the USC Institute of Urology.

In 2017, U.S. News & World Report ranked Keck School of Medicine among the top 35 medical schools in the country.

For more information, go to keck.usc.edu.

ABOUT THE MULTIPLE MYELOMA RESEARCH FOUNDATION (MMRF)

The mission of the Multiple Myeloma Research Foundation (MMRF) is to find a cure for multiple myeloma by relentlessly pursuing innovation that accelerates the development of next-generation treatments to extend the lives of patients. Founded in 1998 by Kathy Giusti, a multiple myeloma patient, and her twin sister Karen Andrews as a 501 (c) (3) nonprofit organization, the MMRF is a world-recognized leader in cancer research. Together with its partners, the MMRF has created the only end-to-end solution in precision medicine and the single largest genomic dataset in all cancers. The MMRF continues to disrupt the industry today, as a pioneer and leader at the helm of new research efforts. Since its inception, the organization has raised over $350 million and directs nearly 90% of the total funds to research and related programs. As a result, the MMRF has been awarded by Charity Navigator's coveted four-star rating for 12 years, the highest designation for outstanding fiscal responsibility and exceptional efficiency.

For more information, go to themmrf.org.

ABOUT TGEN

Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with neurological disorders, cancer, diabetes, and infectious diseases, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. TGen is affiliated with City of Hope, a world-renowned independent research and cancer and diabetes treatment center: www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. For more information, visit: www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.

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