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The link between a cancer diagnosis and one’s genetics has been an important aspect of research for years. Many think of the link in terms of hereditary cases, that is if a type of cancer runs in the family because of a certain gene mutation. But the role of genetics in cancer goes far beyond deciding a person’s inherited risk.
Mesothelioma is known to be caused by exposure to asbestos, but more studies have come out recently that help determine how genetics may influence the disease. Last year, researchers at the International Mesothelioma Program (IMP) published their study on the gene-sequencing of mesothelioma tumors. The study opened the door for the development of more personalized therapies to respond to a specific tumor’s genetic makeup in an individual.
Researchers have also been looking further into the connection between the BAP1 gene and mesothelioma. Researchers found those with the BAP1 gene and a family history of cancer typically developed mesothelioma earlier and had improved long-term survival compared to others. This connection could help lead to earlier detection of the disease and better treatment for future patients.
A new study further investigated the role of genetics in malignant mesothelioma patients under the age of 40. Researchers wanted to learn more about particular gene fusions, how often these fusions occurred, and the clinical symptoms they caused.
Studying Genetics in Malignant Mesothelioma
The study looked at both peritoneal mesothelioma and pleural mesothelioma patients under 40 years old. Researchers looked at the genetics of 25 patients altogether with a median age of 31. The study sought to determine the incidence of rearrangements on the EWSR1 gene in mesothelioma patients, since previous mutations of the gene have been found in older peritoneal mesothelioma patients.
To explore the patient's’ genes, situ hybridization was used. Situ hybridization is a powerful tool that allows a particular nuclei to be localized and obtain information about a gene expression and its positioning on a chromosome. There are two basic ways to study RNA and DNA data in situ hybridization, chromogenic (CISH) and fluorescence (FISH). This study used FISH because it can provide a bigger picture and information for multiple genes at once.
FISH works by using fluorescent probes that bind to particular chromosomes. It can reveal the absence or presence of DNA sequences, or can be used to study RNA targets to reveal gene expression. For this study, researchers made artificial chromosome probes for the EWSR1, FUS, and ATF1 genes. Prior to beginning this clinical trial, researchers had found evidence of an EWSR1-ATF1 gene fusion in 2 malignant mesothelioma cases, and wanted to understand its prevalence, as well as its impact on the symptoms and pathology of the disease.
The researchers also screened for the BAP1 gene when possible, since earlier studies found that the presence of this gene often indicated earlier development of mesothelioma and longer survival than patients who didn’t exhibit the gene mutations.
Finding More Gene Fusions
Through these screenings, researchers found a few different fusions in patients’ genes. In four patients, 16% of the participants, the ATF1 gene was found with the EWSR1 or FUS genes as partners. These gene fusions have previously been linked to other diseases, like clear cell sarcoma.
Of the patients who exhibited one of these gene fusions, researchers also noted their mesothelioma displayed a classic epithelioid morphology. This is the most common cell type of mesothelioma, generally found in 50 - 70% of all mesothelioma cases. Since it is most common, it has also been the most researched to find effective treatments, like immunotherapy and gene therapy. Hopefully, continued studies like this one to further explore the mutations linked with mesothelioma can help make these emerging treatments more effective.
For the patients in which the BAP1 gene could be screened, 3 of the fusion-positive cases demonstrated the gene and 80% of the other participants also exhibited the BAP1 gene. Many studies now have shown BAP1 expression as being a strong risk factor for mesothelioma.
Overall, the researchers explained the study expanded the scope of genetic mutations associated with mesothelioma. This study also gave a unique insight into mesothelioma among younger patients and how genetics may impact their case. Hopefully with further study, researchers can continue to better understand the links between these mutations and mesothelioma tumors.
Genetics and Mesothelioma
While none of us can control or really combat any of these genetic abnormalities, discovering these mutations can still help patients. With further study, it’s possible these genetic mutations could serve as markers for the disease. Overall, this could potentially mean better ways to detect and diagnose mesothelioma earlier, which could have a great positive impact on survival.
Understanding the genetic differences could also help researchers and oncologists explore new treatment options, like the potential of gene therapy. Though there is still a lot of research and development ahead for these treatments and even better understanding mesothelioma, these studies provide hope for longer survival for mesothelioma patients and patients of other cancers displaying gene mutations.