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Recent Advances in the Genomic and Proteomic Researches on Mesothelioma: What Are Novel Insights into Mesothelioma Biology?

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Part of the Respiratory Disease Series: Diagnostic Tools and Disease Managements book series (RDSDTDM)

Abstract

Malignant mesothelioma is an aggressive tumor that has been associated with exposure to asbestos fibers. The discovery that germline heterozygous mutations of the gene encoding the deubiquitylase BRCA-associated protein 1 (BAP1) leads to inheritable higher susceptibility to mesothelioma underscores the relevance of gene x environment (GxE) interactions. Carriers of BAP1 germline mutations are affected by the BAP1 cancer syndrome, a high penetrance Mendelian disorder, characterized by earlier development of mesothelioma and specific types of other cancers. Numerous next-generation sequencing (NGS) analyses have been recently conducted searching for both germline and somatic alterations in patients affected by mesothelioma and associated cancers, and their relatives. BAP1 resulted in the more frequently germline mutated gene; however, other genes involved in DNA repair and homologous recombination were also identified. The pattern of chromothripsis, or chromosome staggering, which has been somatically identified in mesothelioma by several groups, may explain the frequent occurrence of noncontiguous biallelic genome alterations. Moreover, transcriptome studies in mesothelioma showed also the occurrence of fusion transcripts involving tumor suppressor genes. The complete knowledge of the genetic background associated with the GxE interactions involved in the pathogenesis of mesothelioma will be further improved by future genetic and genomic studies, allowing to develop better strategies for the prevention and treatment of this malignancy.

Keywords

  • Mesothelioma
  • BAP1
  • NGS
  • GxE interaction
  • Chromothripsis

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Emi, M., Gaudino, G., Yoshikawa, Y., Ohmuraya, M. (2021). Recent Advances in the Genomic and Proteomic Researches on Mesothelioma: What Are Novel Insights into Mesothelioma Biology?. In: Nakano, T., Kijima, T. (eds) Malignant Pleural Mesothelioma. Respiratory Disease Series: Diagnostic Tools and Disease Managements. Springer, Singapore. https://doi.org/10.1007/978-981-15-9158-7_12

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  • DOI: https://doi.org/10.1007/978-981-15-9158-7_12

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