Different gene mutations in multiple myeloma depending on ancestry

Researchers, based in the US, have conducted a large-scale collection of publicly available data and found that significant differences can be observed in the types of mutations experienced between those of European descent and African Americans diagnosed with multiple myeloma.

Related to this, health outcomes were significantly lower for African Americans compared to Caucasians, despite the common mutations in the former group pointing towards a better prognosis.

Multiple myeloma is a form of blood cancer that affects plasma cells. In the US, approximately 30,000 new cases of multiple myeloma are diagnosed each year and 13,000 patients die from it.

African Americans are three times more likely than Europeans to be diagnosed with multiple myeloma and twice as many individuals die from it, in comparison to Caucasians of the same age and gender.

The researchers did suggest that this could predominantly be identified as due to socioeconomic issues and limited access to better quality medical care. Additionally, treatments developed to treat multiple myeloma are often developed through clinical trials comprising of a majority of individuals of European descent.

New treatments have been developed that have shown improvements in survival rates across the board; however, the treatments have disproportionately boosted survival rates for Caucasian patients – the research points towards a reason why this might be.

"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 tumour suppressor gene," said Zarko Manojlovic, 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."

By comparison, African Americans were more likely to have mutations in the BCL7A, BRWD3 and AUTS2 genes – in a finding that highlighted the role these genes play in multiple myeloma for the first time.

This means that newly developed treatments, due to the lack of inclusion of ethnic minorities in clinical trials, often target gene mutations that will not be as effective outside of the Caucasian majority.

"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, Chair of the Department of Translational Genomics at the Keck School of Medicine and senior author of the paper.

He continued, "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 pursue these observations to better improve clinical management of the disease for all patients."