In Malignant Pleural Mesothelioma, New Mutations in Gene Identified, Potentially Leading to Future Therapies

In Malignant Pleural Mesothelioma, New Mutations in Gene Identified, Potentially Leading to Future Therapies

Frequent mutations in the SETDB1 gene and genome-wide alterations of allelic loss were identified in malignant pleural mesothelioma, according to results of a recent study, “Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas,” published in the Oncotarget journal.

Malignant pleural mesothelioma is a rare, aggressive tumor that forms on the thin protective tissues that cover the lungs and abdomen, and is strongly linked to exposure to high levels of asbestos or other organic fibers. The incidence of the disease is expected to increase in the United States due to its wide use by several industries. However, the underlying genetic mechanisms of malignant pleural mesothelioma development are not fully understood.

A team of researchers used a whole genome sequence approach in a rare case of a patient, a 62-year-old Caucasian woman, who had multiple primary cancers (lung adenocarcinoma and a history of bladder cancer) and malignant pleural mesothelioma. Researchers performed a whole exome sequencing on patient mesothelioma and adjacent normal pleural tissue (control tissue).

Researchers found an established mutation, R282W, in the tumor suppressor gene TP53, and a genome-wide allelic loss or loss of heterozygosity (which occurs when a somatic cell contains only one copy of an allele), with the later genomic alteration not previously described in malignant pleural mesothelioma. Additionally, the team discovered a high frequency of SETDB1 mutations (SETDB1 is a histone methyltransferase) in malignant pleural mesothelioma, a finding further validated by targeted deep-sequencing analysis. Previous studies reported that the SETDB1 gene is amplified and is a potential oncogene (a gene that has the potential to cause cancer) in lung cancer, where increased expression of SETDB1 promotes tumor invasiveness.

The findings indicated that mutations of SETDB1 are a frequent genetic alteration in malignant pleural mesothelioma, which suggests that histone modifier genes are potentially important in this type of cancer. Moreover, the high frequency SETDB1 inactivating mutations suggest its potential value as a new diagnostic marker. Finally, researchers highlighted that future studies should investigate the role of SETDB1 in malignant pleural mesothelioma development and disclose its potential for future therapeutic options.

 

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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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