From the blog

Gene Therapy and DNA Sequencing for Malignant Mesothelioma

Published: January 19, 2018

Genes are the basic unit of DNA that creates unique proteins used for specific cellular function. The expression of that gene creates an effect and if a gene cannot make a specific protein, this can lead some health risks or problems.

A multifactorial disorder, like cancer, heart disease, and diabetes, are the result of multiple gene mutations and environmental factors. Mesothelioma fits the criteria of a multifactorial disorder, but through gene therapy techniques, those suffering from this asbestos-caused disease have a chance of fighting this illness by replacing, removing, introducing, or altering faulty genes.

Once researchers identity the faulty gene and learn about how and why the gene functions as it does, the next step is deliver new information to the genome. Since genes inserted directly into the cell typically have no effect, a carrier – otherwise known as a vector – is used for gene transportation. Believe it or not, one way genes are delivered are through viruses because viruses are essentially drawn to and attack the cell. These viruses are modified and don’t cause any further illness when administered to the patient.

Gene Therapy in Mesothelioma
A cancer cell that originally has this mutated gene that allowed the cell to become cancerous in the first place, receives a new gene. This newly added gene will allow the cancer cell to respond to treatment and hopefully kill the cancer altogether.  In mesothelioma, a virus is injected to the pleural space causing infection in the mesothelioma cells. This new gene that is now in the mesothelioma cell allows the immune system to become effective again in fighting the cancer.

DNA sequencing is used to determine the order of adenine, guanine, cytosine, and thymine in a single strand of DNA.  Knowing the sequence of individual genes in medicine allows medical professionals to determine if a person is at risk for a genetic disease. Even though mesothelioma is deadly, the cancer is overall very rare. Asbestos exposure is the only known cause of mesothelioma, but not everyone who has worked with asbestos will contract an asbestos-related disease. DNA sequencing aims to provide a more definitive answer to those who might be at higher risk.

Next Generation Sequencing
Next Generation Sequencing (aka Next-Gen Sequencing or NGS), is a tool that is able to quickly identify millions upon millions of DNA strands in parallel. For mesothelioma, NGS examines a person’s DNA to find mutations that are common in mesothelioma patients.

In 2016 a study published in the International Journal of Cancer and Research Treatment investigated NGS in patients with pleural and peritoneal mesothelioma. The study was small, consisting of only 11 mesothelioma patients (7 pleural, 4 peritoneal) along with 236 cancer-related mutations analyzed. Overall 73% of the patients had detectable mutations, with more detectable mutations found in those with pleural mesothelioma than with peritoneal.

Mesothelioma can be difficult to diagnose, and with symptoms often not appearing until that later stages of the disease, scientists and researchers are hoping that with technology such as DNA sequencing,they would be able to determine who may be at risk for mesothelioma and allow for more screening tools to be developed.

 

Sources:
Ugurluer, G et. al., “Genome-based Mutational Analysis by Next Generation Sequencing in Patients with Malignant Pleural and Peritoneal Mesothelioma”, International Journal of Cancer Research and Treatment ( May 2016). [Link]

U.S. National Library of Medicine, “How Does Gene Therapy Work?” (January 16, 2018). [Link]

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