Everyone’s genes are slightly different. The differences are grouped into categories, which are called polymorphisms. A gene can be different at a single point—one of the nucleotides which string together the DNA chain of genes and sequences controlling gene function. A single-point difference is called a single-nucleotide polymorphism (SNP).
It is now possible to scan the whole DNA to determine which SNPs are present. One can then see if any of them are linked to a better or poorer outcome for a patient. This process is called genome-wide association studies or GWAS.
For the first time, a GWAS search was used to learn whether any particular SNP correlated with the outcome of myeloma patients. Dr. Elad Ziv and colleagues combined datasets from 306 myeloma patients treated at the University of California, San Francisco and 239 myeloma patients treated at Mayo Clinic. They found that an SNP close to a gene called FOPNL on chromosome 16p13 was linked to poorer survival. This correlation came to attention because the survival difference was 2.7 years! This genetic variation occurred in 14 percent of myeloma patients. As one might suspect, much further work is needed to substantiate and understand this finding, but this initial report published in Nature Communications is quite tantalizing.
The SNP variant of the FOPNL gene is more active, meaning there are increased expression levels. This increased activity can be linked to something called “centrosome amplification,” a process involved with separation of chromosomes during cell division. Problems with the centrosome can lead to chromosome instability, which produces mutations or translocations or extra/missing chromosomes—all common features of myeloma. There is, thus, a sense that the new genetic finding is relevant and important.
Previous studies led by International Myeloma Working Group (IMWG) member and principal investigator of the Asian Myeloma Network (AMN) Clinical Trials Network, Dr. Wee Joo Chng, here and here, have shown a strong correlation between centrosome problems (primarily amplification) and myeloma patient survival.
This is definitely an aspect of genetic research which can turn out to be very important. We already know from two studies, here and here, that the abnormal centrosome processes can be blocked by aurora kinase inhibitors. So, there is hope for a new approach to treatment. Chromosome 16 needs to be added to our list of chromosomes to watch.
As always, stay tuned for further developments!
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.