For the first time, scientists have accessed the molecular causes of multiple myeloma – an aggressive, incurable blood cancer with a 5-year survival rate of 40%.
This week, several multiple myeloma genomes have been sequenced. And they reveal an assortment of mutated genes involved (that have never been suspected before) and identify chemical pathways to target in future therapies – some of which are already in development.
The disease begins in the bone marrow, where white blood cells become malignant (pictured), crowding out normal bone marrow cells and attacking solid bone. There are about 20,000 new cases in the US a year.
To map out its genetic code, researchers sequenced 38 tumor genomes from multiple myeloma patients, and then compared them with the patients’ normal DNA sequences.
"If we compare the tumor genome to the normal genome, that gives us great clues about what makes a normal cell into a cancer cell," explains study coauthor Todd Golub of the Broad Institute in Cambridge, Mass. "We need the ability to look across many cancer genomes and to discover mutations that are recurring at low frequencies, so that we can see patterns emerging from the data that are biologically meaningful,” he adds.
- They found mutations affecting genes that have never been implicated in this cancer – sending the field in a new, unanticipated direction.
“These genes, which are frequently mutated, were not on anyone’s radar before when thinking about multiple myeloma specifically or cancer in general,” says Golub. “This shows that there are entirely new cancer-causing genes that are going to be discovered through these sequencing efforts.”
- More immediately applicable, they found that about 4% of multiple myeloma patients have mutations in the BRAF gene – the same type of mutations found in some people with the skin cancer melanoma.
As MSNBC reports, melanoma patients with this mutation have shown a strong response to an experimental drug being developed by Roche and Daiichi Sankyo's newly acquired Plexxikon.
That means an immediate trial could be done in a subset of multiple myeloma patients using a drug already in late-stage development.
"There had been some speculation that maybe we've discovered all the cancer-causing genes and there's nothing left," Golub says. "The ability to look broadly in this way is showing us that we haven't."
But he emphasizes: “This has been made possible not by our brilliance but by advances in new gene sequencing technology.”
Next-generation sequencing allows scientists to comprehensively analyze the cancer genome at high resolutions and “see all of the events that happen in cancer,” adds study coauthor Gad Getz of the Broad Institute. “Now, we can find those genes whose mutations occur more than expected by chance.”
"Five years from now,” Golub says, “we will have the genetic landscape of all common human cancers mapped out."
The report appeared in Nature yesterday.