The Multiple Myeloma Research Foundation (MMRF) today hailed a new publication in Nature as a major step forward in the organization’s efforts to advance a personalized medicine approach in multiple myeloma. Researchers at the Eli and Edythe L. Broad Institute of Harvard and MIT today published an analysis of 38 multiple myeloma genome sequences – the largest such data set ever published on multiple myeloma. The authors uncovered novel connections between multiple myeloma and important molecular targets, at least one of which could have immediate clinical significance. Drugs against this target are already showing promise in melanoma, underscoring the potential importance of these findings for cancer types beyond multiple myeloma.
The work was conducted as part of the Multiple Myeloma Genomics Initiative (MMGI), a genome-mapping program supported by the Multiple Myeloma Research Foundation (MMRF) to significantly advance biological understanding of the disease. The analysis was conducted using a combination of whole-genome sequencing and whole-exome sequencing, performed on patient samples gathered via the Multiple Myeloma Research Consortium (MMRC), a network of 16 collaborating academic medical centers, and organized into a centralized tissue bank. Funding for the project, which is ongoing, comes from the MMRF.
“It is critical to improve our understanding of the complex biology of multiple myeloma in order to accelerate the development of next-generation treatments, and eventually find a cure,” said Kathy Giusti, Founder and CEO of the MMRF and MMRC, and a multiple myeloma patient. “Our vision is that upon diagnosis, patients will have access to a range of treatments, chosen based on individualized insights from a patient’s molecular profile. Today’s publication is an important step toward that goal, and a foundation upon which the scientific community can build to help improve the treatment of patients with multiple myeloma and other cancers.”
The Nature paper describes connections between multiple myeloma and several molecular pathways, including those associated with protein production and epigenetic regulation (histone methylation). Additionally, oncogenic mutations were seen in the kinase BRAF, which was not previously associated with multiple myeloma, but which is a therapeutic target in clinical trials for melanoma. A follow-up analysis revealed that 4% of 161 multiple myeloma samples harbored a BRAF mutation, including the specific BRAF mutation that is the target of the drug being developed in melanoma by Roche and Plexxikon (PLX4032). Beyond the specific implications for multiple myeloma, the results underscore the valuable role that large sample cancer genome sequencing can play in uncovering new insights into cancer not anticipated by existing knowledge.
Todd Golub, M.D., Director of the Broad Institute’s Cancer Program and Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute and principal author on the study, said: “The vast majority of the discoveries highlighted in our paper today would not have been possible by sequencing only a single multiple myeloma genome, underscoring the vital role that this initiative is playing in elucidating the processes involved in multiple myeloma. These findings are a testament to the vision and effectiveness of the MMRF’s efforts in genomics and personalized medicine, which have rapidly advanced to become an invaluable resource to the broad scientific community.”
Multiple Myeloma Research Foundation