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What Is Malignant Mesothelioma?

Types of Mesothelioma CancerMalignant Mesothelioma is a tumor associated with exposure to mineral fibers such as asbestos and erionite. 1 In spite of stringent regulations introduced in the 1970s and 80s to limit asbestos exposure, the incidence of Malignant Mesothelioma reached 3,200 cases per year in the US in 2003 and it has remained stable since then. 2 The incidence of Malignant Mesothelioma has also sharply increased worldwide over the past 50 years. 1

Malignant Mesothelioma is an almost uniformly fatal malignancy. 1

While early detection is associated with better responses to therapy and prolonged survival 3 over 90% of Malignant Mesotheliomas are diagnosed at a late stage, when survival may only be extended by ~11 weeks with the standard of care. 3 Thus, to make an impact on the disease, there is a critical need to understand etiology and develop diagnostics for early detection of Malignant Mesothelioma, particularly in high-risk cohorts. There is a long latency of 20-60 years between initial exposure to mineral fibers and Malignant Mesothelioma development, which provides opportunities for prevention, early detection or intervention at the early stages of disease, provided that interventions and reliable biomarkers for exposure and early detection are available. 1

Malignant Mesothelioma can appear in several areas of the body:

  • Pleura - The most frequently occurring type of Malignant Mesothelioma. The tumor affects the pleural lining, which is a thin layer of tissue that lines the chest and chest wall. About 75% of all Malignant Mesotheliomas diagnosed are pleural based.
  • Peritoneum - The peritoneum is a lining of cells surrounding the abdominal cavity. About 20 - 25% of Malignant Mesotheliomas are peritoneal.
  • Pericardium - The tumor invades the pericardial lining that surrounds the heart. This is a very rare type of Malignant Mesothelioma.
  • Testes (in males) - This extremely rare form of Malignant Mesothelioma affects the membrane that surrounds the testes.

Dr. Carbone’s research aims at finding ways to easily diagnose Malignant Mesothelioma in extremely early stages, even before an individual experiences symptoms of the disease. Simple blood and saliva tests are being developed to identify individuals at risk of developing mesothelioma and some other types of cancer associated with a genetic alteration of BAP1. By detecting at-risk individuals sooner, and identifying their cancer at the earliest possible phase, there is hope for longer, more comfortable life, as well as hope for an eventual cure.

REFERENCES

  1. Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. Malignant mesothelioma: Facts, myths and hypotheses. Malignant mesothelioma: Facts, myths and hypotheses. Journal of  Cellular Physiology, 227: 44-58, 2012 Jan. PMCID: PMC3143206.
  2. Henley SJ, Larson TC, Wu M, et al. Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003-2008. International Journal of Occupational and Environmental Health 2013;19:1-10.
  3. Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M, Bains MS, Rusch VW. Extrapleural Pneumonectomy Versus Pleurectomy Decortication in the Surgical Management of Malignant Pleural Mesothelioma. Journal of Thoracic Cardiovascular Surgery, 2008.
  4. Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, Gaudino G, Jube S, Kanodia S, Partridge CR, Pass HI, Rivera ZS, Steele I, Tuncer M, Way S, Yang H, Miller A. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proceedings of the National Academy of Science USA, 108:13618-23, 2011.
  5. Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler D, and Carbone M. The presence of asbestos in the natural environment is likely related to mesothelioma in young individuals and women from Southern Nevada. Journal of Thoracic Oncology, 10:731-7, 2015.
  6. Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, Bianchi ME, and Carbone M. Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proceedings of the National Academy of Science USA, 107: 12611-12616, 2010. PMCID: PMC2906549.
  7. Carbone M, Emri S, Dogan U, Steele I, Tuncer M, Pass HI, Baris YI. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nature Reviews Cancer, 7:147-154, 2007.
  8. Roushdy-Hammady I, Siegel J, Emri S, Testa JR and Carbone M. A genetic-susceptibility factor malignant mesothelioma in the Cappadocian region of Turkey. The Lancet, 357:444-445, 2001.
  9. Dogan UA, Baris YI, Dogan M, Emri S, Steele I, Elmishad AG, and Carbone M. Genetic Predisposition to Fiber Carcinogenesis Causes a mesothelioma Epidemic in Turkey. Cancer Research, 66:5063-5068, 2006.
  10. Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox N, Dogan AU, Pass, HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, and Carbone M. Germline BAP1 mutations predispose to malignant mesothelioma. Nature Genetics, 43: 1022-25, 2011.
  11. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. Bap1 and cancer. Nature Review Cancer, 13:153-159, 2013.
  12. Napolitano A, Pellegrini L, Dei A, Larson D, Tanji M, Flores EG, Kendrick B, Lapid D, Powers A, Kanodia S, Pastorino S, Pass HI, Dixit V, Yang H, and Carbone M. Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene, Advance online publication, June 29, 2015.
  13. Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nature Genetics, 2012;44:751-759.
  14. Carbone M, Ferris LK, Baumann F, Napolitano A, Lum CA, Flores EG, Gaudino G, Powers A, Bryant-Greenwood  P, Krausz T, Hyjek E, Tate R, Friedberg J, Weigel T, Pass HI, Yang H.  BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs.  Journal of Translational Medicine, 10:179, 2012.
  15. Baumann F, Flores E, Napolitano A, Kanodia A, Taioli E, Pass H, Yang H, and Carbone M. Mesothelioma Patients with Germline BAP1 Mutations Have Seven-Fold Improved Long-term Survival. Carcinogenesis, 36:76-81, 2015.
  16. Carbone M, Flores EG, Emi M, Johnson TA, Tsunoda T, Behner D, Hoffman H, Hesdorffer M, Nasu M, Napolitano A, Power A, Minaai M, Baumann F, Bryant-Greenwood P, Lauk O, Kirschner MB, Weder W, Opitz I, Pass HI, Gaudino G, Pastorino S, Yang H. Combined genetic and genealogic studies uncover a large BAP1 cancer syndrome kindred, tracing back nine generations to a common ancestor from the 1700s. PLoS Genetics, Advance online publication, Dec 18, 2015
  17. Napolitano A, Antoine DJ , Pellegrini L, Baumann F, Pagano IS , Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, Carbone M.  and Yang H. HMGB1 and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clinical Cancer Research, Advance online publication, Jan 5, 2016.
  18. Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Baumann F, Zhang YA, Gazdar A, Kanodia S, Tiirikainen M, Flores E, Gaudino G, Becich GJ, Pass HI, Yang H, and Carbone M. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. Journal of Thoracic Oncology, 10:565-76, 2015.
  19. Carbone M., et al. Consensus Report of the 2015 Weinman International Conference on Mesothelioma. Journal of Thoracic Oncology, accepted
  20. Carbone M and Yang H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clinical Cancer Research, 18:598-604, 2012.
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