Asbestos and mesothelioma: genetic lessons from a tragedy

Our plain-English summary of Asbestos and mesothelioma: genetic lessons from a tragedy, by A. Knudson (Proceedings of the National Academy of Sciences of the United States of America, 1995).

The study

• Author: A. Knudson
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Published: 1995;92(24):10819-20
• Type of article: Comment, Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

In this commentary, the author discussed what malignant mesothelioma, an uncommon tumor of the pleural and peritoneal surfaces associated in the vast majority of cases with asbestos fibers, revealed about the genetics of cancer. He noted that smoking produced a synergistically high incidence of lung cancer among asbestos-exposed people but not a significantly higher incidence of mesothelioma. He reviewed reported genetic changes in mesothelioma. These were loss of chromosome 9p with loss or mutation of the CDKN2 (p16) gene, TP53 mutations in some tumors, mutations of the Wilms tumor gene WT1, and monosomy 22, which removes the neurofibromatosis type 2 (NF2) tumor suppressor gene. He discussed a report in the same issue by Bianchi et al., which found NF2 mutations in 8 of 15 cell lines and in 6 matching tumors, all predicting truncation of the protein. He described the 40% incidence as clearly significant. He asked why mesothelioma is not a feature of hereditary NF2. He suggested that in renewal tissues such as mesothelium some pathological condition must stimulate stem cell proliferation, and that asbestos fibers seemed to provide this stimulus. Citing a rat model in which asbestos acted like a tumor promoter, he proposed that asbestos may act epigenetically and may cause chromosome missegregation, with mutations accumulating over many years. He concluded that studying this asbestos-linked tumor was teaching lessons about carcinogenesis.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a short commentary that reported no new data of its own. The author discussed genetic research on malignant mesothelioma, a tumor of the mesothelial surfaces (linings) of the pleural and peritoneal cavities, which the author linked to asbestos fibers in most cases. The commentary mainly introduced a study by Bianchi and colleagues in the same journal issue. As the author described it, that study found mutations in the NF2 gene in 8 of 15 mesothelioma cell lines and in 6 matching tumors. The author called a 40% incidence clearly significant and said the true figure could be higher. The author noted that an earlier study had found such mutations in only one primary tumor. The author also said it was not clear how NF2 mutations contribute to the cancer, and that the inherited disease neurofibromatosis type 2 does not predispose to mesothelioma. Citing other work, the author said asbestos does not appear to act as a mutagen but can disrupt how chromosomes separate when cells divide. The author proposed a possible sequence of events: asbestos stimulates cell growth, and genetic changes then build up over many years.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Commentary (opinion and discussion piece); no original data
• Who was studied: No study population of its own. The commentary discussed published genetic studies of mesothelioma, chiefly the study by Bianchi et al. in the same journal issue.
• Exposure: Asbestos fibers in general. No specific fiber type was named. The author also mentioned the widespread use of asbestos in shipbuilding during World War II.
• Main results:
  • Reported by Bianchi et al., not by this article: NF2 mutations in 8 of 15 mesothelioma cell lines and in 6 matching tumors. The author called a 40% incidence clearly significant and said the true percentage could be still higher.
  • Reported by Sekido et al., not by this article: NF2 mutations in some cell lines but in only one primary tumor.
  • The author stated that it is not clear how NF2 mutations contribute to the development of mesothelioma.
  • The author noted that the hereditary disease neurofibromatosis type 2 does not predispose to mesothelioma.
  • Citing other work, the author stated that asbestos does not appear to act as a mutagen. According to that work, asbestos can interact with the mitotic spindle and cause chromosome missegregation and aneuploidy.
  • The author proposed a possible scenario, not a tested finding: one copy of the NF2 gene would be mutated and the other lost by monosomy (loss of a whole chromosome).
• The authors' conclusion: The author concluded that studying mesothelioma is teaching about how cancer develops. The author suggested that asbestos itself may have an epigenetic effect (one that does not change the genes themselves) equivalent to that produced elsewhere by genetic change.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Lung Cancer, Tumor Suppressor Gene, Mesothelium, STEM, Carcinogenesis.

Related studies

• Translocation (3;3)(p14;q29) as the primary chromosome abnormality in a peritoneal mesothelioma — M.R. Teixeira, K.E. Giercksky, et al. (1998)
• Asbestos: Socio-legal and Scientific Controversies and Unsound Science in the Context of the Worldwide Asbestos Tragedy - Lessons to be Learned — X. Baur (2016)
• Molecular and genetic changes in asbestos-related lung cancer — P. Nymark, H. Wikman, et al. (2008)
• Malignant pleural mesothelioma: newer aspects of carcinogenesis, molecular genetics, and prospects for future therapies — J.S. Donington, D.J. Mew, et al. (1995)
• Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma — S.S. Murthy, J.R. Testa (1999)
• Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma — M. Tiainen, L. Tammilehto, et al. (1989)

Browse more research in Proceedings of the National Academy of Sciences of the United States of America, or return to medical research.