The therapeutic implications of the genomic analysis of malignant pleural mesothelioma

Our plain-English summary of The therapeutic implications of the genomic analysis of malignant pleural mesothelioma, by M.G. Zauderer (Nature Communications, 2021).

The study

• Author: M.G. Zauderer
• Journal: Nature Communications
• Published: 2021;12(1):1819
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Delineation of the genomic complexities of malignant pleural mesothelioma (MPM) has lagged behind other malignancies. Zhang et al. meaningfully add to our understanding of MPM, and their findings emphasize the need to combine drug development efforts with appropriate predictive biomarkers.

In plain English

This article was a short commentary, not an original study. The author discussed a separate study by Zhang et al., published in the same journal in 2021, on the genetics of malignant pleural mesothelioma (MPM). As the author described it, Zhang et al. sequenced 90 tumor samples taken during surgery (extended pleurectomy/decortication) from 22 patients with MPM. They found wide genetic variation both between patients and within single tumors. Tumor evolution followed a linear pattern in 64% of cases and a branched pattern in the other 36%. Changes in the BAP1 gene appeared to occur early and changes in NF2 late. Detectable circulating free DNA in the blood was associated with worse survival, and the most highly branched tumors had higher T-cell infiltration. The author noted that the drug combination ipilimumab plus nivolumab had received FDA approval, but that no compelling predictive marker had been identified to help choose treatment. The author concluded that future clinical trials need to focus on predictive biomarkers for new therapies. The article did not discuss asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Commentary (opinion piece) on another group's study (Zhang et al., Nature Communications 2021); not original research
• Who was studied: No patients were studied in this article. The commentary describes Zhang et al.'s study of 90 tumor samples from 22 patients with MPM, collected at extended pleurectomy/decortication
• Main results:
  • As reported by the author, Zhang et al. found extensive variation between patients and within individual tumors
  • As reported by the author, in Zhang et al.'s study linear evolutionary trees modeled 64% of cases (branched trees the remaining 36%)
  • As reported by the author, Zhang et al.'s analysis suggested BAP1 events occur early in MPM evolution and NF2 events occur late
  • As reported by the author, Zhang et al. demonstrated clonal positive selection for NF2, BAP1, SETD2, FBXW7 and PRELID1
  • As reported by the author, in Zhang et al.'s study 24% of samples had copy number alterations, and only 5% of these were subclonal
  • As reported by the author, in Zhang et al.'s study detectable circulating free DNA was associated with inferior survival
  • As reported by the author, in Zhang et al.'s study the most highly branched tumors had higher T-cell infiltration
  • The author noted that ipilimumab plus nivolumab had received FDA approval for MPM
  • The author stated that no compelling predictive marker to guide treatment selection had been identified
• The authors' conclusion: The author concluded that future clinical trials need to focus on predictive biomarkers for novel therapies in MPM

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker.

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• Insights Into Genomic Drivers, Transcriptomic Heterogeneity, and Therapeutic Vulnerabilities From Novel Mesothelioma Cell Lines — Y. Wu, F. Cao, et al. (2026)
• Syntenic relationships between genomic profiles of fiber-induced murine and human malignant mesothelioma — D. Jean, E. Thomas, et al. (2011)
• Cancer genomics of lung cancer including malignant mesothelioma: A brief overview of current status and future prospects — S.C. Jhanwar, X.L. Xu, et al. (2020)
• Cyclin Pathway Genomic Alterations Across 190,247 Solid Tumors: Leveraging Large-Scale Data to Inform Therapeutic Directions — D.L. Jardim, S.Z. Millis, et al. (2021)

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