The rare and deadly form of cancer known as mesothelioma has proven extremely challenging to researchers and physicians, who have been largely unable to stop the progress or significantly improve survival.
A study using targeted next-generation sequencing of malignant pleural mesothelioma tumor provided a partial explanation of why the cancer has been so immutable. It showed that mesothelioma has a complex mutational setting including a high number of genetic alterations in the genes associated with the disease.
These genes are involved in cell survival, cell proliferation pathways and DNA repair, and the high number of different mutations involved greatly contribute to the disease’s progression, as well as its resistance to treatment.
Malignant pleural mesothelioma has an extremely low survival rate. After three years, the mean survival rate is only eight percent. Much of this is due to the fact that mesothelioma has such a long latency period. Most patients don’t exhibit symptoms of their disease until it is already in an advanced stage and there are limited treatment options available.
By using next-generation sequencing, researchers from the University of Torino, Orbassano, Italy, and Saint Antonio and Biagio General Hospital in Alessandria, Italy, were able to focus on the mesothelioma genes to identify the genetic mutations within. They published their results in the “Journal of Thoracic Oncology.”
Their study showed that in malignant pleural mesothelioma DNA, there are two specific pathways in which mutations cluster. The mutations were in genes that are supposed to enable DNA repair and to decrease the time of disease progression, as well as overall survival, and there was evidence of multiple mutations in each.
There was also a mutation in the BAP1 gene, which lead to changes in the cell’s amino acids.
“Our results show that NGS is clearly feasible despite the very well-known challenges of fragmented and low-yield DNA isolated from FFPE tumor tissue,” they write.
“Our data did not identify any specific mutation as a single driver gene, as found in adenocarcinoma of the lung, however our data suggests that in malignant pleural mesothelioma there is an accumulation of several non-driver mutations, which may explain the extremely long latency phase of this asbestos-related disease.”
The scientists suggest that future clinical trials could focus on targeted therapies that address each of these genetic mutations.