Different Types of Mesothelioma Show Distinct Frequencies of Gene Mutations, Study Finds

Different Types of Mesothelioma Show Distinct Frequencies of Gene Mutations, Study Finds

Different types of malignant mesothelioma (MM) may be associated with different frequencies of gene mutations, according to a new study published in the journal Modern Pathology.

In the study, “Genomic Profiling Of Malignant Peritoneal Mesothelioma Reveals Recurrent Alterations In Epigenetic Regulatory Genes BAP1, SETD2, And DDX3X,” the authors identify several mutations that are found at different rates in malignant pleural mesothelioma and malignant peritoneal mesothelioma and that can serve as potential markers.

Malignant mesothelioma is a rare type of cancer that affect the pleural cavity (the protective lining of the lung) in more than 80 percent of cases. In peritoneal mesothelioma, it affects the lining of the abdomen, mainly in women. Mesothelioma could also affect the pericardial lining, which protects the heart, and the tunica vaginalis, which covers the testes.

Current treatments for mesothelioma are limited, and there is still a need for more and better options. For this reason, knowing which molecules contribute to the development and aggressiveness of the disease in patients may provide useful information for the design of novel therapeutic strategies.

However, genetic alterations that drive peritoneal mesothelioma may be different from those in pleural mesothelioma.

Researchers analyzed 510 cancer-associated genes in a group of 13 patients with peritoneal mesothelioma. The team noticed that 11 patients presented a decrease in the expression levels of the BAP1 gene, which is involved in multiple cellular processes like proliferation, differentiation, cell death, and DNA repair mechanisms. This decrease was associated with either mutations or deletions in the gene.

Loss of BAP1 was confirmed in all cases by staining the corresponding protein in samples of cancer cells from the patients. The two tumors without BAP1 alteration and an additional 42 cases of peritoneum diseases (other than peritoneal mesothelioma) had intact BAP1 staining. This result accounts for the specificity of BAP1 protein loss as a helpful diagnostic marker for the pathologic identification of malignant peritoneal mesotheliomas.

Besides BAP1, other genes were found to be mutated in this group of patients, namely NF2 (three of the 13); SETD2 (two of the 13); and DDX3X (two of the 13). Although these genes have been previously associated with pleural mesothelioma, the frequency with which they occur in peritoneal mesothelioma was found to be different.

“While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20–30% of pleural tumors,” the researchers wrote.

“Together, these findings demonstrate the importance of [certain genes] including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies,” they added.

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