Understanding the Underlying Causes of Peritoneal Mesothelioma

There is new evidence that alterations in the expression of certain genes, also known as epigenetics, may play an even bigger role in malignant peritoneal mesothelioma than in pleural mesothelioma.

Both forms of malignant mesothelioma, an aggressive cancer that impacts internal membranes, are associated with exposure to asbestos, but the association is strongest with pleural mesothelioma.

That led researchers in the Clinical Cancer Genomics Lab and the Department of Pathology at the University of California to take a closer look at the gene-related mechanisms that may underlie peritoneal mesothelioma and how they impact disease development and prognosis.

The team sequenced 510 cancer-related genes in 13 patients with malignant peritoneal mesothelioma.

Gene Expression and Malignant Mesothelioma

Gene expression is the mechanism by which cells, including mesothelioma tumor cells, regulate all kind of processes, from growth and replication, to metabolism, programmed death, and recycling of cellular components.

When certain genes are expressed in irregular ways, the cells receive irregular or unusual messages. Mutations in certain genes can cause mesothelioma cells to grow and spread out of control, migrate to other parts of the body, “hide” from the immune system, and resist treatment.

Frequent BAP1 Alteration in Peritoneal Mesothelioma

One important finding from the new University of California study is that nearly 85 percent of patients with peritoneal mesothelioma were found to have tumors with alterations of the BAP1 tumor suppressor gene.

In contrast, only 20 to 30 percent of pleural mesothelioma cases have been associated with BAP1 alteration, the most frequent altered gene in peritoneal mesothelioma patients.

Other Genes Also Altered

BAP1 expression was not the only anomaly the researchers found in the cells of patients with peritoneal mesothelioma.

Other mutated genes seen among these 13 patients included NF2, which is believed to play a role in controlling cell shape, movement and communication, SET2, and DDX3X.

“Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies,” writes pathologist and researcher Dr. Nancy Joseph in a recent issue of Modern Pathology.

This kind of research is made possible by a relatively new technology known as gene sequencing, which is the process of determining the order of nucleotides in a DNA molecule. It is increasingly being used to better understand hard-to-treat cancers like malignant mesothelioma.

Fewer than a third of all mesothelioma cases that occur in the US each year are of the peritoneal variety.

Source:

Joseph, NM, et al, “Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X”, November 4, 2016, Modern Pathology,