Molecular pathogenesis of malignant mesothelioma



The underlying molecular alterations in MM have not yet been clearly determined despite the massive efforts of independent laboratories or collaboration efforts. It was a truly surprising discovery that MM can develop as a familial cancer syndrome with the BAP1 germline mutation. Although there are still many important unanswered questions, newly developed molecular analytical tools continue to unveil the key cellular events including genetic and epigenetic alterations, which can be applied for target therapy. Differences in individual susceptibility of MM among asbestos exposures of a similar level and duration need to be more precisely determined in order to establish a more effective preventive strategy. Thus, a complete understanding of the molecular pathogenetic changes of MM is critically needed to develop more effective approaches for identifying and treating this devastating disease.

Acknowledgments

The author is keenly aware of the vast amount of excellent scientific contributions to the field and wishes to apologize to all colleagues whose work could not be cited due to space limitations.

Neurofibromatosis type 2 inactivation

The neurofibromatosis type 2 ( NF2 ) gene encodes a tumor suppressor protein, merlin (moesin-ezrin-radixin-like protein), a member of the Band 4.1 family of cytoskeletal linker proteins. NF2 cancer syndrome is characterized by the development of tumors of the nervous system such as bilateral vestibular schwannomas at the eighth cranial nerve, spinal schwannomas, and meningiomas. Biallelic NF2 mutations are also frequently detected in sporadic cases of these tumors.

Conclusions

The underlying molecular alterations in MM have not yet been clearly determined despite the massive efforts of independent laboratories or collaboration efforts. It was a truly surprising discovery that MM can develop as a familial cancer syndrome with the BAP1 germline mutation. Although there are still many important unanswered questions, newly developed molecular analytical tools continue to unveil the key cellular events including genetic and epigenetic alterations, which can be applied for target therapy. Differences in individual susceptibility of MM among asbestos exposures of a similar level and duration need to be more precisely determined in order to establish a more effective preventive strategy. Thus, a complete understanding of the molecular pathogenetic changes of MM is critically needed to develop more effective approaches for identifying and treating this devastating disease.

Abbreviations:

  • ARF

    alternative reading frame

  • BAP1

    BRCA1-associated protein-1

  • CDKN2A

    cyclin-dependent kinase inhibitor 2A

  • FISH

    fluorescence in situ hybridization

  • HPMCs

    human peritoneal mesothelial cells

  • miR

    micro RNA

  • MM

    malignant mesothelioma

  • MPM

    malignant pleural mesothelioma

  • mTOR

    mammalian target of rapamycin

  • MWCNTs

    multiwalled carbon nanotubes

  • NF2

    neurofibromatosis type 2

  • PI3K

    phosphoinositide-3 kinase

  • RTK

    receptor tyrosine kinase

  • TSG

    tumor suppressor gene.



Tags: