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Genetic Predisposition to Mesothelioma: What Are the Biological Mechanisms and What Are the Clinical Characteristics of These Mesotheliomas?

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Malignant Pleural Mesothelioma

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Abstract

Mesothelioma has been for many years the example of a malignancy induced exclusively by exposure to the environmental carcinogen asbestos. In recent years additional fibers, erionite and antigorite for example, and therapeutic ionizing radiation have been shown to cause mesothelioma. Most importantly, molecular genetic studies conducted by our team revealed that inactivating mutations of the BAP1 gene predispose individuals to mesothelioma. At times these mutations cause mesothelioma in combination with exposure to asbestos or to other carcinogens. Recent studies revealed that at least 12% of mesotheliomas develop in carriers of germline BAP1 mutations or, less frequently, of mutations of other tumor suppressor genes: these patients have a prolonged survival of 5 or more years. Thus mesothelioma has now become the preferred model to study gene x environment (GxE) interaction in human cancer. Genetic testing has become routine for mesothelioma patients in most major research hospitals and it is hoped that soon all patients will be tested to identify possible germline mutations as well tumor-specific mutations that can inform therapy. Moreover, family members of patients carrying BAP1 mutations can be tested, and if positive for mutations, they can be enrolled in early detection clinical trials that are often life-saving.

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References

  1. Carbone M, Adusumilli PS, Alexander HR Jr, Baas P, Bardelli F, Bononi A, et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019;69(5):402–29.

    Article  PubMed  Google Scholar 

  2. Delgermaa V, Takahashi K, Park EK, Le GV, Hara T, Sorahan T. Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. Bull World Health Organ. 2011;89(10):716–24, 24A–24C.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Henley SJ, Larson TC, Wu M, Antao VC, Lewis M, Pinheiro GA, et al. Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003–2008. Int J Occup Environ Health. 2013;19(1):1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bridda A, Padoan I, Mencarelli R, Frego M. Peritoneal mesothelioma: a review. MedGenMed. 2007;9(2):32.

    PubMed  PubMed Central  Google Scholar 

  5. Lee M, Alexander HR, Burke A. Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy. Pathology. 2013;45(5):464–73.

    Article  CAS  PubMed  Google Scholar 

  6. Mao W, Zhang X, Guo Z, Gao Z, Pass HI, Yang H, et al. Association of asbestos exposure with malignant mesothelioma incidence in Eastern China. JAMA Oncol. 2017;3(4):562–4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Carbone M, Kanodia S, Chao A, Miller A, Wali A, Weissman D, et al. Consensus report of the 2015 Weinman international conference on mesothelioma. J Thorac Oncol. 2016;11(8):1246–62.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Baumann F, Ambrosi JP, Carbone M. Asbestos is not just asbestos: an unrecognised health hazard. Lancet Oncol. 2013;14(7):576–8.

    Article  PubMed  Google Scholar 

  9. Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler DJ, Carbone M. The presence of asbestos in the natural environment is likely related to mesothelioma in young individuals and women from Southern Nevada. J Thorac Oncol. 2015;10(5):731–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Baumann F, Carbone M. Environmental risk of mesothelioma in the United States: an emerging concern-epidemiological issues. J Toxicol Environ Health B Crit Rev. 2016;19(5–6):231–49.

    Article  CAS  PubMed  Google Scholar 

  11. Wylie AG, Candela PA. Methodologies for determining the sources, characteristics, distribution, and abundance of asbestiform and nonasbestiform amphibole and serpentine in ambient air and water. J Toxicol Environ Health B Crit Rev. 2015;18:1):1–42.

    Article  PubMed  Google Scholar 

  12. Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, et al. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci USA. 2011;108(33):13618–23.

    Article  CAS  PubMed  Google Scholar 

  13. Qi F, Okimoto G, Jube S, Napolitano A, Pass HI, Laczko R, et al. Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-alpha signaling. Am J Pathol. 2013;183(5):1654–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ramos-Nino ME, Blumen SR, Sabo-Attwood T, Pass H, Carbone M, Testa JR, et al. HGF mediates cell proliferation of human mesothelioma cells through a PI3K/MEK5/Fra-1 pathway. Am J Respir Cell Mol Biol. 2008;38(2):209–17.

    Article  CAS  PubMed  Google Scholar 

  15. Hillegass JM, Shukla A, Lathrop SA, MacPherson MB, Beuschel SL, Butnor KJ, et al. Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model. Ann N Y Acad Sci. 2010;1203:7–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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 USA. 2010;107(28):12611–6.

    Article  CAS  PubMed  Google Scholar 

  17. Xu A, Zhou H, Yu DZ, Hei TK. Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species. Environ Health Perspect. 2002;110(10):1003–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carbone M, Klein G, Gruber J, Wong M. Modern criteria to establish human cancer etiology. Cancer Res. 2004;64(15):5518–24.

    Article  CAS  PubMed  Google Scholar 

  19. Larson D, Powers A, Ambrosi JP, Tanji M, Napolitano A, Flores EG, et al. Investigating palygorskite’s role in the development of mesothelioma in southern Nevada: insights into fiber-induced carcinogenicity. J Toxicol Environ Health B Crit Rev. 2016;19(5–6):213–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Napolitano A, Pellegrini L, Dey A, Larson D, Tanji M, Flores EG, et al. Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene. 2016;35(15):1996–2002.

    Article  CAS  PubMed  Google Scholar 

  21. Sluis-Cremer GK. Asbestos disease at low exposures after long residence times. Ann N Y Acad Sci. 1991;643:182–93.

    Article  CAS  PubMed  Google Scholar 

  22. Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, et al. Malignant mesothelioma: facts, myths, and hypotheses. J Cell Physiol. 2012;227(1):44–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science (New York, NY). 2008;320(5876):674–7.

    Article  CAS  Google Scholar 

  24. Chow MT, Tschopp J, Moller A, Smyth MJ. NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma. Immunol Cell Biol. 2012;90(10):983–6.

    Article  CAS  PubMed  Google Scholar 

  25. Carbone M, Yang H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin Cancer Res. 2012;18(3):598–604.

    Article  CAS  PubMed  Google Scholar 

  26. Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, et al. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012;72(13):3290–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mezzapelle R, Rrapaj E, Gatti E, Ceriotti C, Marchis FD, Preti A, et al. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells. Sci Rep. 2016;6:22850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu JY, Brass DM, Hoyle GW, Brody AR. TNF-alpha receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers. Am J Pathol. 1998;153(6):1839–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, et al. TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci USA. 2006;103(27):10397–402.

    Article  CAS  PubMed  Google Scholar 

  30. Chen Z, Gaudino G, Pass HI, Carbone M, Yang H. Diagnostic and prognostic biomarkers for malignant mesothelioma: an update. Transl Lung Cancer Res. 2017;6(3):259–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tabata C, Kanemura S, Tabata R, Masachika E, Shibata E, Otsuki T, et al. Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma. J Clin Gastroenterol. 2013;47(8):684–8.

    Article  CAS  PubMed  Google Scholar 

  32. Tabata C, Shibata E, Tabata R, Kanemura S, Mikami K, Nogi Y, et al. Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma. BMC Cancer. 2013;13:205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ostroff RM, Mehan MR, Stewart A, Ayers D, Brody EN, Williams SA, et al. Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool. PLoS One. 2012;7(10):e46091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Emri SA. The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad. Ann Transl Med. 2017;5(11):239.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 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.

    Article  CAS  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43(10):1022–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Carbone M, Ferris LK, Baumann F, Napolitano A, Lum CA, Flores EG, et al. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med. 2012;10:179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Haugh AM, Njauw CN, Bubley JA, Verzi AE, Zhang B, Kudalkar E, et al. Genotypic and phenotypic features of BAP1 cancer syndrome: a report of 8 new families and review of cases in the literature. JAMA Dermatol. 2017;153(10):999–1006.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Walpole S, Pritchard AL, Cebulla CM, Pilarski R, Stautberg M, Davidorf FH, et al. Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide. J Natl Cancer Inst. 2018;110(12):1328–41.

    Article  PubMed  PubMed Central  Google Scholar 

  43. 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:Jco2018790352.

    Google Scholar 

  44. 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.

    Article  CAS  Google Scholar 

  45. 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 USA. 2019;116(18):9008–13.

    Article  CAS  PubMed  Google Scholar 

  46. Baumann F, Flores E, Napolitano A, Kanodia S, Taioli E, Pass H, et al. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival. Carcinogenesis. 2015;36(1):76–81.

    Article  CAS  PubMed  Google Scholar 

  47. Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet. 2011;43(10):1018–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Piris A, Mihm MC Jr, Hoang MP. BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations. Hum Pathol. 2015;46(2):239–45.

    Article  CAS  PubMed  Google Scholar 

  49. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mutti L, Peikert T, Robinson BWS, Scherpereel A, Tsao AS, de Perrot M, et al. Scientific advances and new frontiers in mesothelioma therapeutics. J Thorac Oncol. 2018;13(9):1269–83.

    Article  PubMed  PubMed Central  Google Scholar 

  52. McCambridge AJ, Napolitano A, Mansfield AS, Fennell DA, Sekido Y, Nowak AK, et al. Progress in the management of malignant pleural mesothelioma in 2017. J Thorac Oncol. 2018;13(5):606–23.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 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 USA. 2016;113(47):13432–7.

    Article  CAS  PubMed  Google Scholar 

  54. Mashtalir N, Daou S, Barbour H, Sen NN, Gagnon J, Hammond-Martel I, et al. Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Mol Cell. 2014;54(3):392–406.

    Article  CAS  PubMed  Google Scholar 

  55. Ismail IH, Davidson R, Gagne JP, Xu ZZ, Poirier GG, Hendzel MJ. Germline mutations in BAP1 impair its function in DNA double-strand break repair. Cancer Res. 2014;74(16):4282–94.

    Article  CAS  PubMed  Google Scholar 

  56. Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S, et al. Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci USA. 2014;111(1):285–90.

    Article  CAS  PubMed  Google Scholar 

  57. Yu H, Mashtalir N, Daou S, Hammond-Martel I, Ross J, Sui G, et al. The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Mol Cell Biol. 2010;30(21):5071–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bononi A, Giorgi C, Patergnani S, Larson D, Verbruggen K, Tanji M, et al. BAP1 regulates IP3R3-mediated Ca(2+) flux to mitochondria suppressing cell transformation. Nature. 2017;546(7659):549–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhang Y, Shi J, Liu X, Feng L, Gong Z, Koppula P, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol. 2018;20(10):1181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bononi A, Yang H, Giorgi C, Patergnani S, Pellegrini L, Su M, et al. Germline BAP1 mutations induce a Warburg effect. Cell Death Differ. 2017;24(10):1694–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Okonska A, Bühler S, Rao V, Ronner M, Blijlevens M, IVd M-M, et al. Genome-wide silencing screen in mesothelioma cells reveals that loss of function of BAP1 induces chemoresistance to ribonucleotide reductase inhibition: implication for therapy. bioRxiv. 2018:381533.

    Google Scholar 

  62. Guazzelli A, Meysami P, Bakker E, Demonacos C, Giordano A, Krstic-Demonacos M, et al. BAP1 status determines the sensitivity of malignant mesothelioma cells to gemcitabine treatment. Int J Mol Sci. 2019;20(2):429.

    Article  PubMed Central  Google Scholar 

  63. 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.

    Article  CAS  PubMed  Google Scholar 

  64. 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.

    Article  CAS  PubMed  Google Scholar 

  65. 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.

    Article  CAS  PubMed  Google Scholar 

  66. Ugurluer G, Chang K, Gamez ME, Arnett AL, Jayakrishnan R, Miller RC, et al. Genome-based mutational analysis by next generation sequencing in patients with malignant pleural and peritoneal mesothelioma. Anticancer Res. 2016;36(5):2331–8.

    CAS  PubMed  Google Scholar 

  67. Kratzke RA, Otterson GA, Lincoln CE, Ewing S, Oie H, Geradts J, et al. Immunohistochemical analysis of the p16INK4 cyclin-dependent kinase inhibitor in malignant mesothelioma. J Natl Cancer Inst. 1995;87(24):1870–5.

    Article  CAS  PubMed  Google Scholar 

  68. Micolucci L, Akhtar MM, Olivieri F, Rippo MR, Procopio AD. Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis. Oncotarget. 2016;7(36):58606–37.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Carbone M, Rizzo P, Pass H. Simian virus 40: the link with human malignant mesothelioma is well established. Anticancer Res. 2000;20(2a):875–7.

    CAS  PubMed  Google Scholar 

  70. Gazdar AF, Carbone M. Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40. Clin Lung Cancer. 2003;5(3):177–81.

    Article  PubMed  Google Scholar 

  71. Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad AG, Vacek P, et al. Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Natl Acad Sci USA. 2006;103(38):14128–33.

    Article  CAS  PubMed  Google Scholar 

  72. Dang-Tan T, Mahmud SM, Puntoni R, Franco EL. Polio vaccines, simian virus 40, and human cancer: the epidemiologic evidence for a causal association. Oncogene. 2004;23(38):6535–40.

    Article  CAS  PubMed  Google Scholar 

  73. Klein G, Powers A, Croce C. Association of SV40 with human tumors. Oncogene. 2002;21(8):1141–9.

    Article  CAS  PubMed  Google Scholar 

  74. Carbone M, Pannuti A, Zhang L, Testa JR, Bocchetta M. A novel mechanism of late gene silencing drives SV40 transformation of human mesothelial cells. Cancer Res. 2008;68(22):9488–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhang L, Qi F, Gaudino G, Strianese O, Yang H, Morris P, et al. Tissue tropism of SV40 transformation of human cells: role of the viral regulatory region and of cellular oncogenes. Genes Cancer. 2010;1(10):1008–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Goodman JE, Nascarella MA, Valberg PA. Ionizing radiation: a risk factor for mesothelioma. Cancer Causes Control. 2009;20(8):1237–54.

    Article  PubMed  Google Scholar 

  77. Chirieac LR, Barletta JA, Yeap BY, Richards WG, Tilleman T, Bueno R, et al. Clinicopathologic characteristics of malignant mesotheliomas arising in patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(36):4544–9.

    Article  Google Scholar 

  78. Farioli A, Ottone M, Morganti AG, Compagnone G, Romani F, Cammelli S, et al. Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database. Cancer Med. 2016;5(5):950–9.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Barsky AR, Friedberg JS, Culligan M, Sterman DH, Alley E, Litzky LA, et al. Radiation-induced malignant mesothelioma: frequency and prognosis: mesothelioma, thymic malignancies, and other thoracic malignancies. Int J Radiat Oncol Biol Phys. 2014;90(5):S27–S8.

    Article  Google Scholar 

  80. Kittaneh M, Berkelhammer C. Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members. J Transl Med. 2018;16(1):194.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Carbone M, Arron ST, Beutler B, Bononi A, Cavenee W, Cleaver JE, Croce CM, D’Andrea A, Foulkes WD, Gaudino G, Groden JL, Henske EP, Hickson ID, Hwang PM, Kolodner RD, Mak TW, Malkin D, Monnat RJ, Jr., Novelli F, Pass HI, Petrini JH, Schmidt LS, Yang H. Tumour predisposition and cancer syndromes as models to study gene-environment interactions. Nature reviews Cancer. 2020. Epub 2020/05/31. https://doi.org/10.1038/s41568-020-0265-y. PubMed PMID: 32472073.

  82. Carbone M, Harbour JW, Brugarolas J, Bononi A, Pagano I, Dey A, Krausz T, Pass HI, Yang H, Gaudino G. Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer. Cancer Discov. 2020;10(8):1103–20. Epub 2020/07/22. https://doi.org/10.1158/2159-8290.CD-19-1220. PubMed PMID: 32690542.

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Acknowledgments

We thank all the family members affected by the “BAP1 cancer syndrome” and the patients with BAP1-mutated tumors that donated their specimens. They allowed us to study and discover how this gene functions in different cancer types and to translate this knowledge to improve cancer prevention, diagnosis, and prognosis [already being implemented), and in the near future, we hope, to improve therapies for patients with BAP1-mutated cancers.

Financial Support and Disclosures

M.C. and H. Y. report grants from the National Institutes of Health 1R01CA198138; 1R01CA237235; 1R01ES030948, the US Department of Defense CA150671P1, and the UH Foundation through donations to support research on “Pathogenesis of Malignant Mesothelioma” from Honeywell International Inc, Riviera United-4-a Cure, and the Maurice and Joanna Sullivan Family Foundation and the Germaine Hope Brennan Foundation. M.C. has a patent issued for BAP1. M.C and H.Y. have a patent issued for “Using Anti-HMGB1 Monoclonal Antibody or other HMGB1 Antibodies as a Novel Mesothelioma Therapeutic Strategy,” and a patent issued for “HMGB1 As a Biomarker for Asbestos Exposure and Mesothelioma Early Detection.” M.C. is a board-certified pathologist who provides consultation for mesothelioma expertise and diagnosis, including paid consulting.

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

    Michele Carbone, Michael Minaai, Sandra Pastorino & Haining Yang

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  1. Michele Carbone
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  2. Michael Minaai
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Correspondence to Michele Carbone .

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

    Takashi Nakano

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

    Takashi Kijima

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Carbone, M., Minaai, M., Pastorino, S., Yang, H. (2021). Genetic Predisposition to Mesothelioma: What Are the Biological Mechanisms and What Are the Clinical Characteristics of These Mesotheliomas?. 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_13

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