Identification of Genes Involved With MM Development Could Mean More Personalized Treatments

There are 40 genes involved with the development of multiple myeloma (MM), according to new research published in Leukemia. The discovery increases the understanding of the complex genetics behind the disease, which is currently incurable, and could lead to the development of more personalized treatments.

The authors explained that “so far the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown,” and identifying driver mutations would be “fundamental to understanding MM oncogenesis and its response to therapy.”

The team of researchers, who were based at The Institute of Cancer Research in London, United Kingdom, and mostly funded by Myeloma UK, uncovered new areas of coding and noncoding DNA that drive early progression of MM.

“We need smarter, kinder treatments for myeloma that are more tailored to each person's cancer,” Richard Houlston, FRS, FMedSci, professor of Molecular and Population Genetics at The Institute of Cancer Research, said in a statement. “Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

The researchers analyzed whole-exome sequencing data from 804 people with MM and whole-genome sequencing data from 765 people with MM. Overall, 16 genes were disrupted in coding regions of DNA and 15 were disrupted in noncoding areas.

The research also highlighted that pathways key to the development of MM can be targeted through a range of mechanisms. While upregulation of MYC through gene amplification or translocation is established in MM, it can be dysregulated by other mechanisms, such as by copy number variation altering MYC noncoding regulatory regions.

The authors concluded by writing that a more “comprehensive picture of the underlying genetic basis of MM” can lead to an extended list of genes and pathways for which a network-based drug search may identify novel therapeutics.

“This new research is a valuable step forward in our understanding of the complex genetic changes which drive myeloma,” said Simon Ridley, PhD, director of research at Myeloma UK.

Reference

Hoang PH, Dobbins SE, Cornish AJ, et al. Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms [published online April 9, 2018]. Leukemia. doi: 10.1038/s41375-018-0103-3.