During a recent study, researchers sequenced the genomes of 38 multiple myeloma patients and identified a number of genetic mutations that may contribute to the onset of multiple myeloma.  These findings may help researchers develop improved therapies for myeloma.

Scientists from 21 of the leading research institutes in the United States and Canada contributed to this new genome study that will be published on Thursday in the journal Nature.

The study is important because “it gives insight into the biology of a disease, which we are only beginning to understand,” said Dr. David S. Siegel, one of the study investigators and chief of the myeloma division at the John Theurer Cancer Center in Hackensack, New Jersey.

In multiple myeloma, as with all cancers, cells develop genetic abnormalities known as “mutations.” These mutations can lead to uncontrolled growth and survival of the cells.  In multiple myeloma, mutations result in growth of blood cells that produce abnormal antibodies, thus leading to a weakened immune system.

In this study, researchers used genome sequencing to better understand the mechanisms underlying the development of multiple myeloma.  In genome sequencing, the exact makeup of a patient’s genetic information can be determined.  By comparing the genomic sequence of a healthy cell to the sequence of a cancerous cell, mutations can be identified and studied.

Unlike other studies, which have sequenced the genome of an individual myeloma patient, this study analyzed cells from 38 patients.  These sequences could then be used to identify patterns that could not be seen in the smaller, single patient studies.

The researchers confirmed that mutations previously reported in three genes of myeloma patients were present in the current study population.  In addition, researchers also identified many new genes that have not been previously known to be involved in cancer.

“The more targets we can identify, the more tools we can develop to treat the disease.  The more specific the tools are, the less toxicity that should be associated with their use,” said Dr. Siegel.

In nearly half the patients, mutations were found in genes responsible for the production of proteins.  Mutations were also found in genes responsible for blood clotting and the control of DNA within the cell.

Additionally, genes in the NF-Kappa-B pathway were mutated in 11 patients.  The NF-Kappa-B pathway regulates the division and death of cells.  This finding confirms previous work that showed the NF-Kappa-B protein is overly abundant in multiple myeloma patients.

Another important observation is that 4 percent of patients had a mutation in the BRAF protein pathway, which is involved in cell growth.  A number of drugs to inhibit the BRAF protein are currently under development, particularly for the treatment of melanoma.  Researchers in the study noted that their findings indicate that these drugs should be evaluated for possible use as multiple myeloma treatments.

“The next step will be to increase the number of samples and to correlate the results with the clinical behavior. What is the difference between a smoldering patient and one with aggressive disease?” said Dr. Siegel. “The other critical next step is the serial sequencing of individual patients. We need to learn what new mutations lead to the development of drug resistance, more aggressive behavior, and to new complications.”

For more information, see the study in Nature ^[1] and press releases from the John Theurer Cancer Center ^[2] and the Broad Institute of MIT and Harvard ^[3].