New gene sequencing technique developed by University of Michigan researchers reveals that metastasized tumors have many more mutations.

With the advent of personalized medicines, there is significant potential to offer individualized treatments for people suffering from many different types of diseases. Researchers at the University of Michigan hope to develop personalized treatments for patients that suffer from cancers that have spread or metastasized. To do so, however, more information is needed on why solid tumors spread, which requires more details about their genetic makeup than can be obtained using existing, commercially available genetic analysis methods.

Their solution was to develop a new gene sequencing technique for solid tumors. The method involves sequencing both the DNA and RNA from biopsies of metastatic tumors. Analysis of RNA is a crucial component of the technique because RNA is present in tumor microenvironments and is involved in biochemical processes that result in the activation of cancer-causing genes and the inhibition of genes designed to fight cancer. Analyzing RNA, therefore, enables investigation of the immune cells surrounding the tumors, information that could potentially be used to identify patients that could benefit from immunotherapy. 

To evaluate the effectiveness of the new sequencing technique, the scientists analyzed samples taken from 500 patients enrolled in the Michigan Oncology Sequencing Program whose cancers had metastasized. Not only the primary tumors, but tumors that had spread beyond the point of origin of the cancer (including over 30 types of cancer from 22 organs) were tested. The tumors that had spread were found in nearly all of the patients to have much higher numbers and more different types of mutations compared to those observed in the primary tumors. The researchers hypothesize that cancer cells develop more mutations over time as they spread throughout the body and are exposed to different chemotherapy drugs.

"Tumors are evolving as part of metastasis and under therapy,” said Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. “We need to biopsy the metastatic tumors and then suggest therapies, rather than using archival tissue from the primary tumor."

The scientists also discovered when comparing tumor DNA to normal DNA that 12% of the patients in the study had an inherited mutation, and of those mutations, 75% were associated with DNA repair, which is a target for a number of marketed cancer treatments. The results suggest that relatives of patients with metastatic solid tumors and inherited mutations may want to consider having genetic testing performed to determine their risk for cancer. 

The next phase of the study will involve analysis of the treatment outcomes of the patients in order to identify any existing treatment or potential new drug targets. Early results indicate that 75% of the patients could benefit from commercially available drugs.