In a recent study, an international research team reported several new genetic mutations that may be involved in multiple myeloma. Additionally, the researchers identified genetic changes associated with disease progression.

Dr. Niccolo Bolli from the University of Cambridge in the United Kingdom presented the findings last month at the 17th Congress of the European Hematology Association (EHA).

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 cancer cells.  In multiple myeloma, mutations typically result in the growth of white blood cells that produce abnormal antibodies, thus leading to a weakened immune system.

Genome sequencing can be used to determine the exact makeup of a patient’s genetic information (scientifically referred to as DNA).  By comparing the genomic sequence of a healthy cell to the sequence of a cancerous cell, mutations can be identified and studied.

Once mutations associated with multiple myeloma are identified, researchers can develop new treatments targeted at those mutations.

Because myeloma patients generally have different combinations of mutations, the ability to identify a patient’s mutations along with the development of targeted treatments could ultimately lead to more individualized therapy for myeloma patients.

The full genome of a myeloma cell was first sequenced in 2009 (see related Beacon ^[1] news).  Since then, researchers have continued to sequence the genomes of myeloma cells from more patients to better understand which genetic mutations are responsible for multiple myeloma (see related Beacon ^[2] news).

In the continued quest to better understand the genetic variances responsible for the onset and progression of myeloma, Dr. Bolli and his colleagues sequenced the genomes of 68 multiple myeloma patients. Additionally, multiple DNA samples from 17 of the patients were gathered at different time points, ranging from five to 18 months apart.

The researchers identified 1,803 genes that were mutated in the patients' myeloma cells; 292 of the genes were mutated in multiple patients, suggesting that they play a role in myeloma.  The mutations included some of those previously identified by myeloma genome sequencing studies, but several new gene mutations also were identified as being involved in myeloma.

Overall, 97 percent of patients had at least two sets of myeloma cells with different genetic mutations at diagnosis.  These results suggest that myeloma is not only a heterogeneous disease across patients, but that each patient has heterogeneous disease.

Of the patients who provided multiple DNA samples available, 80 percent demonstrated shifts over time in the amount of myeloma cells with certain genetic mutations. Additionally, 60 percent of patients acquired more chromosomal additions or deletions.  Of these, 44 percent eventually showed evidence of a deleted region in chromosome 17 (known as 17p deletion). The 17p deletion is categorized as a high-risk abnormality that commonly leads to poorer survival outcomes.   These results suggest that the new mutations in later samples play a role in disease progression.

For more information, particularly about the different types of genes that were mutated, please see abstract 571 ^[3] on the EHA Meeting ^[4] website.