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Malignant Pleural Mesothelioma pp 137–149Cite as

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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References

  1. Franke K, Paustenbach D. Government and navy knowledge regarding health hazards of asbestos: a state of the science evaluation (1900 to 1970). Inhal Toxicol. 2011;23(Suppl 3):1–20. https://doi.org/10.3109/08958378.2011.643417.

    CAS  CrossRef  PubMed  Google Scholar 

  2. Sluis-Cremer GK, Liddell FD, Logan WP, Bezuidenhout BN. The mortality of amphibole miners in South Africa, 1946–80. Br J Ind Med. 1992;49(8):566–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Lanphear BP, Buncher CR. Latent period for malignant mesothelioma of occupational origin. J Occup Med. 1992;34(7):718–21.

    CAS  PubMed  Google Scholar 

  4. Linton A, Vardy J, Clarke S, van Zandwijk N. The ticking time-bomb of asbestos: its insidious role in the development of malignant mesothelioma. Crit Rev Oncol Hematol. 2012;84(2):200–12. https://doi.org/10.1016/j.critrevonc.2012.03.001.

    CrossRef  PubMed  Google Scholar 

  5. Carbone M, Adusumilli PS, Alexander HRJ, Baas P, Bardelli F, Bononi A, et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019;69:402–29. https://doi.org/10.3322/caac.21572.

    CrossRef  PubMed  Google Scholar 

  6. Baumann F, Ambrosi JP, Carbone M. Asbestos is not just asbestos: an unrecognised health hazard. Lancet Oncol. 2013;14(7):576–8. https://doi.org/10.1016/S1470-2045(13)70257-2.

    CrossRef  PubMed  Google Scholar 

  7. Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, et al. Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci U S A. 2010;107(28):12611–6. https://doi.org/10.1073/pnas.1006542107.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  8. Carbone M, Yang H. Mesothelioma: recent highlights. Ann Transl Med. 2017;5(11):238. https://doi.org/10.21037/atm.2017.04.29.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  9. Carbone M, Emri S, Dogan AU, Steele I, Tuncer M, Pass HI, et al. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nat Rev Cancer. 2007;7(2):147–54. https://doi.org/10.1038/nrc2068.

    CAS  CrossRef  PubMed  Google Scholar 

  10. Roushdy-Hammady I, Siegel J, Emri S, Testa JR, Carbone M. Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey. Lancet. 2001;357(9254):444–5. https://doi.org/10.1016/S0140-6736(00)04013-7.

    CAS  CrossRef  PubMed  Google Scholar 

  11. Carbone M, Flores EG, Emi M, Johnson TA, Tsunoda T, Behner D, et al. Combined genetic and genealogic studies uncover a large BAP1 Cancer syndrome kindred tracing Back nine generations to a common ancestor from the 1700s. PLoS Genet. 2015;11(12):e1005633. https://doi.org/10.1371/journal.pgen.1005633.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  12. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13(3):153–9.

    CAS  CrossRef  Google Scholar 

  13. Jensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene. 1998;16(9):1097–112.

    CAS  CrossRef  Google Scholar 

  14. Ventii KH, Devi NS, Friedrich KL, Chernova TA, Tighiouart M, Van Meir EG, et al. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res. 2008;68(17):6953–62. https://doi.org/10.1158/0008-5472.CAN-08-0365.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  15. Betti M, Aspesi A, Ferrante D, Sculco M, Righi L, Mirabelli D, et al. Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes. Genes Chromosomes Cancer. 2018;57(11):573–83. https://doi.org/10.1002/gcc.22670.

    CAS  CrossRef  PubMed  Google Scholar 

  16. Betti M, Casalone E, Ferrante D, Aspesi A, Morleo G, Biasi A, et al. Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma. Cancer Lett. 2017;405:38–45. https://doi.org/10.1016/j.canlet.2017.06.028.

    CAS  CrossRef  PubMed  Google Scholar 

  17. Pastorino S, Yoshikawa Y, Pass HI, Emi M, Nasu M, Pagano I, et al. A subset of mesotheliomas with improved survival occurring in carriers of BAP1 and other Germline mutations. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36:3485–94. https://doi.org/10.1200/jco.2018.79.0352.

    CAS  CrossRef  Google Scholar 

  18. Panou V, Gadiraju M, Wolin A, Weipert CM, Skarda E, Husain AN, et al. Frequency of Germline mutations in cancer susceptibility genes in malignant mesothelioma. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36(28):2863–71. https://doi.org/10.1200/jco.2018.78.5204.

    CAS  CrossRef  Google Scholar 

  19. Hassan R, Morrow B, Thomas A, Walsh T, Lee MK, Gulsuner S, et al. Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Proc Natl Acad Sci U S A. 2019; https://doi.org/10.1073/pnas.1821510116.

  20. Bertelsen B, Tuxen IV, Yde CW, Gabrielaite M, Torp MH, Kinalis S, et al. High frequency of pathogenic germline variants within homologous recombination repair in patients with advanced cancer. NPJ Genom Med. 2019;4:13. https://doi.org/10.1038/s41525-019-0087-6.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  21. Flores RM. Induction chemotherapy, extrapleural pneumonectomy, and radiotherapy in the treatment of malignant pleural mesothelioma: the memorial Sloan-Kettering experience. Lung Cancer. 2005;49(Suppl 1):S71–4. https://doi.org/10.1016/j.lungcan.2005.03.015.

    CrossRef  PubMed  Google Scholar 

  22. Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, et al. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10(4):565–76. https://doi.org/10.1097/JTO.0000000000000471.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  23. Yoshikawa Y, Sato A, Tsujimura T, Emi M, Morinaga T, Fukuoka K, et al. Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 2012;103(5):868–74. https://doi.org/10.1111/j.1349-7006.2012.02223.x.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  24. Guo G, Chmielecki J, Goparaju C, Heguy A, Dolgalev I, Carbone M, et al. Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma. Cancer Res. 2015;75(2):264–9. https://doi.org/10.1158/0008-5472.can-14-1008.

    CAS  CrossRef  PubMed  Google Scholar 

  25. Lo Iacono M, Monica V, Righi L, Grosso F, Libener R, Vatrano S, et al. Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study. J Thorac Oncol. 2015;10(3):492–9. https://doi.org/10.1097/jto.0000000000000436.

    CAS  CrossRef  PubMed  Google Scholar 

  26. Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43(7):668–72. https://doi.org/10.1038/ng.855.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  27. Eckel-Passow JE, Serie DJ, Cheville JC, Ho TH, Kapur P, Brugarolas J, et al. BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor. BMC Urol. 2017;17(1):19. https://doi.org/10.1186/s12894-017-0209-3.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  28. Chirac P, Maillet D, Lepretre F, Isaac S, Glehen O, Figeac M, et al. Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array. Hum Pathol. 2016;55:72–82. https://doi.org/10.1016/j.humpath.2016.04.015.

    CAS  CrossRef  PubMed  Google Scholar 

  29. Yoshikawa Y, Emi M, Hashimoto-Tamaoki T, Ohmuraya M, Sato A, Tsujimura T, et al. High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma. Proc Natl Acad Sci U S A. 2016;113(47):13432–7. https://doi.org/10.1073/pnas.1612074113.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  30. Ly P, Cleveland DW. Rebuilding chromosomes after catastrophe: emerging mechanisms of chromothripsis. Trends Cell Biol. 2017;27(12):917–30. https://doi.org/10.1016/j.tcb.2017.08.005.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  31. Mansfield AS, Peikert T, Smadbeck JB, Udell JBM, Garcia-Rivera E, Elsbernd L, et al. Neoantigenic potential of complex chromosomal rearrangements in mesothelioma. J Thorac Oncol. 2019;14(2):276–87. https://doi.org/10.1016/j.jtho.2018.10.001.

    CAS  CrossRef  PubMed  Google Scholar 

  32. Bjorkqvist AM, Tammilehto L, Anttila S, Mattson K, Knuutila S. Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma. Br J Cancer. 1997;75(4):523–7. https://doi.org/10.1038/bjc.1997.91.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  33. Hagemeijer A, Versnel MA, Van Drunen E, Moret M, Bouts MJ, van der Kwast TH, et al. Cytogenetic analysis of malignant mesothelioma. Cancer Genet Cytogenet. 1990;47(1):1–28. https://doi.org/10.1016/0165-4608(90)90258-c.

    CAS  CrossRef  PubMed  Google Scholar 

  34. Taguchi T, Jhanwar SC, Siegfried JM, Keller SM, Testa JR. Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res. 1993;53(18):4349–55.

    CAS  PubMed  Google Scholar 

  35. Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, et al. Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Lab Investig. 2010;90(3):360–73. https://doi.org/10.1038/labinvest.2009.140.

    CAS  CrossRef  PubMed  Google Scholar 

  36. Nabeshima K, Matsumoto S, Hamasaki M, Hida T, Kamei T, Hiroshima K, et al. Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations. Diagn Cytopathol. 2016;44(9):774–80. https://doi.org/10.1002/dc.23501.

    CrossRef  PubMed  Google Scholar 

  37. Hamasaki M, Matsumoto S, Abe S, Hamatake D, Kamei T, Hiroshima K, et al. Low homozygous/high heterozygous deletion status by p16 FISH correlates with a better prognostic group than high homozygous deletion status in malignant pleural mesothelioma. Lung Cancer. 2016;99:155–61. https://doi.org/10.1016/j.lungcan.2016.07.011.

    CrossRef  PubMed  Google Scholar 

  38. Bianchi AB, Mitsunaga SI, Cheng JQ, Klein WM, Jhanwar SC, Seizinger B, et al. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci U S A. 1995;92(24):10854–8. https://doi.org/10.1073/pnas.92.24.10854.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  39. Sekido Y, Pass HI, Bader S, Mew DJ, Christman MF, Gazdar AF, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55(6):1227–31.

    CAS  PubMed  Google Scholar 

  40. Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, et al. LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer Res. 2011;71(3):873–83. https://doi.org/10.1158/0008-5472.CAN-10-2164.

    CAS  CrossRef  PubMed  Google Scholar 

  41. Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48(4):407–16. https://doi.org/10.1038/ng.3520.

    CAS  CrossRef  PubMed  Google Scholar 

  42. Panagopoulos I, Thorsen J, Gorunova L, Haugom L, Bjerkehagen B, Davidson B, et al. Fusion of the ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X;22-translocation. Genes Chromosomes Cancer. 2013;52(7):610–8. https://doi.org/10.1002/gcc.22057.

    CAS  CrossRef  PubMed  Google Scholar 

  43. Hung YP, Dong F, Watkins JC, Nardi V, Bueno R, Dal Cin P, et al. Identification of ALK rearrangements in malignant peritoneal mesothelioma. JAMA Oncol. 2018;4(2):235–8. https://doi.org/10.1001/jamaoncol.2017.2918.

    CrossRef  PubMed  Google Scholar 

  44. Bruno R, Ali G, Giannini R, Proietti A, Lucchi M, Chella A, et al. Malignant pleural mesothelioma and mesothelial hyperplasia: a new molecular tool for the differential diagnosis. Oncotarget. 2017;8(2):2758–70. https://doi.org/10.18632/oncotarget.13174.

    CrossRef  PubMed  Google Scholar 

  45. De Rienzo A, Richards WG, Yeap BY, Coleman MH, Sugarbaker PE, Chirieac LR, et al. Sequential binary gene ratio tests define a novel molecular diagnostic strategy for malignant pleural mesothelioma. Clin Cancer Res. 2013;19(9):2493–502. https://doi.org/10.1158/1078-0432.CCR-12-2117.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  46. Lo Russo G, Tessari A, Capece M, Galli G, de Braud F, Garassino MC, et al. MicroRNAs for the diagnosis and management of malignant pleural mesothelioma: a literature review. Front Oncol. 2018;8:650. https://doi.org/10.3389/fonc.2018.00650.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  47. van Zandwijk N, Pavlakis N, Kao SC, Linton A, Boyer MJ, Clarke S, et al. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. Lancet Oncol. 2017;18(10):1386–96. https://doi.org/10.1016/S1470-2045(17)30621-6.

    CrossRef  PubMed  Google Scholar 

  48. Hmeljak J, Sanchez-Vega F, Hoadley KA, Shih J, Stewart C, Heiman D, et al. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov. 2018;8(12):1548–65. https://doi.org/10.1158/2159-8290.Cd-18-0804.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Hyogo College of Medicine, Nishinomiya, Japan

    Mitsuru Emi, Yoshie Yoshikawa & Masaki Ohmuraya

  2. University of Hawai’i Cancer Center, Honolulu, HI, USA

    Mitsuru Emi & Giovanni Gaudino

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  1. Mitsuru Emi
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  2. Giovanni Gaudino
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  3. Yoshie Yoshikawa
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  4. Masaki Ohmuraya
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Correspondence to Mitsuru Emi .

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Editors and Affiliations

  1. Center Respiratory Medicine, Otemae Hospital, Osaka, Japan

    Prof. Takashi Nakano

  2. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Prof. Takashi Kijima

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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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