Multiple Myeloma Study Reveals Genetic Landscape of the Disease

A recent study looks at the genetic landscape and the complications behind the blood cancer multiple myeloma.

According to researchers, the study shows that an individual patient's tumor can hold various populations of cancer cells that are equipped with different mutations.

"What this new work shows us is that when we treat an individual patient with multiple myeloma, it's possible that we're not just looking at one disease, but at many - in the same person, there could be cancer cells with different genetic make-ups," said co-senior author Todd Golub, the Broad Institute's Chief Scientific Officer and Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute, via a press release. Golub is also a professor at Harvard Medical School and an investigator at Howard Hughes Medical Institute. "These findings indicate a need to identify the extent of genetic diversity within a tumor as we move toward precision cancer medicine and genome-based diagnostics."

The study authors examined the samples of more than 200 multiple myeloma patients, as well as identified frequent mutations in several key genes that are known to play a critical role in cancers, including KRAS, NRAS, and BRAF. They found that many of the signs of mutations were not always present in cancer cells with a tumor. However, there were a smaller fraction of cells, known as a subclonal population.

The researchers also performed follow-up experiments in the lab in order to explore therapeutic implications by looking specifically at BRAF, a cancer gene that contains several inhibitors or drugs.

"There's clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others," said co-first author Jens Lohr an associated scientist at the Broad and a medical oncologist at Dana-Farber. "If a patient has a BRAF mutation in less than 100 percent of his cells, or if he has mutations in KRAS or NRAS at the same time, his oncologist would want to think through the potential pitfalls before giving the inhibitor."

This new research highlights how subclonal populations could be one of the potential reasons that patients suffer relapses after treatment. However, this problem is not unique to multiple myeloma. Therefore researchers are applying the same techniques to explore other forms of cancer in order to study populations of cancer that look genetically diverse within a single tumor cell.

"In order to appropriately choose targeted therapy, we have to have those studies," said Lohr. "Matching the right drug to the right patient isn't as easy as finding a mutation and having a drug that targets it. We have to keep this additional parameter of heterogeneity in mind."

More information regarding the study can be found via the journal Cancer Cell.