Oncogenes and tumor-suppressor genes in mesothelioma--a synopsis

Our plain-English summary of Oncogenes and tumor-suppressor genes in mesothelioma--a synopsis, by J.F. Lechner, J. Tesfaigzi, B.I. Gerwin (Environmental Health Perspectives, 1997).

The study

• Authors: J.F. Lechner, J. Tesfaigzi, B.I. Gerwin
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1061-7
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Invariably mesothelioma is diagnosed late in the development of the disease when treatment is no longer effective. Therefore, a key to reducing the mortality rate of this neoplasm is knowledge of the general sequence of genetic events between initiation of mesothelial cells and the emergence of the metastatic tumor cells. Unfortunately, relatively little is known about the early changes in the genesis of this disease. Of the known changes, the most frequent are in the tumor-suppressor genes p16INK4a and NF2 and possibly the SV40 virus large T-antigen oncogene. The molecular nature of the changes in these genes as well as other alterations are addressed in this overview.

In plain English

This article is a review of published research on gene changes in mesothelioma. It was based on a 1996 scientific meeting presentation on fibers and particles. The authors reported no new data. They summarized other studies, mostly of human mesothelioma tumors and cell lines. They cited reports that chromosome region 9p13 to p22 is deleted in 50% of mesotheliomas. Studies differed on how often p16INK4a was lost. One study found a homozygous deletion of p16INK4a (both copies lost) in 85% of cell lines but only 22% of primary tumors. Another found p16INK4a and p15INK4b both deleted in more than 70% of primary tumors. NF2 gene changes were reported as frequent in mesotheliomas but rare in lung carcinomas. The authors noted inconsistent data on PDGF and its receptor, p53, WT1 and the possible role of SV40 virus infection. They concluded that the molecular biology of these tumors is not significantly different from cancers attributed to non-fiber carcinogens; only the particular set of genetic changes seems to differ. They said information is limited and offered reasons for the conflicting results.

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: Review (narrative overview) of published studies on tumor-suppressor genes and oncogenes in mesothelioma; no new data
• Who was studied: Published studies, mostly of human mesothelioma tumors and mesothelioma cell lines, with some rodent data; the paper was based on a presentation at a meeting held in Lake Placid, New York, in September 1996
• Exposure: Fiber (asbestos) exposure in general as the background to mesothelioma; the review does not analyze specific fiber types or doses
• Main results:
  • Cytogenetic analyses cited in the review showed chromosome bands 9p13 to p22 deleted in 50% of mesotheliomas
  • Cheng et al. reported a homozygous p16INK4a deletion in 85% of the mesothelial cell lines studied but in only 22% of primary tumors
  • Xiao and co-workers reported both p16INK4a and p15INK4b deleted in more than 70% of primary mesotheliomas
  • For p53, Metcalf et al. found point mutations in only 2 of 20 mesothelioma cell lines, and 1 line did not transcribe p53
  • Carbone et al. reported SV40 T-antigen by immunohistochemistry in 79% of the mesotheliomas examined
  • Metcalf et al. found no SV40 T-antigen in any of 20 mesothelioma cell lines
  • NF2 gene mutations and small deletions were reported as often present in mesothelioma cell lines and primary mesotheliomas, but rare in human lung carcinomas
  • In cited transfection experiments, overexpression of the PDGF-A chain turned the immortal but non-tumor-forming human mesothelial cell line MeT-5A tumor-forming
• The authors' conclusion: The authors concluded that the molecular biology of fiber-associated mesothelioma does not differ significantly from cancers attributed to non-fiber carcinogens; only the particular set of genetic changes seems to differ. Published models propose that losses of chromosomes 6q, 1p and 22q may be among the earliest events.
• Limitations the authors state:
  • Relatively little is known about the early genetic changes in mesothelioma
  • The available data are inconsistent on the form of PDGF and its receptor, on p53 and WT1 status, and on the role of SV40 infection
  • The authors suggested the discrepancies may come from species differences, different routes of fiber exposure, and new changes arising while cell lines were being developed

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Neoplasm, Mesothelial Cells, SV40.

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