Cytogenetic analysis of malignant mesothelioma

Our plain-English summary of Cytogenetic analysis of malignant mesothelioma, by A. Hagemeijer, M.A. Versnel, E. Van Drunen, et al (Cancer Genetics and Cytogenetics, 1990).

The study

• Authors: A. Hagemeijer, M.A. Versnel, E. Van Drunen, M. Moret, M.J. Bouts, T.H. van der Kwast, H.C. Hoogsteden
• Journal: Cancer Genetics and Cytogenetics
• Published: 1990;47(1):1-28
• Cited by: 91 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cytogenetic analyses of 40 confirmed malignant mesotheliomas (MMs) are reported. Pleural effusion cells were studied in 90% of the cases by direct method or after culture or both. Biopsy and ascites fluid were also analyzed in some patients. A normal karyotype was found in nine cases, and complex karyotypic abnormalities were observed in 30 cases. In one case, analyzable metaphases were not obtained. The chromosomal changes were all complex and heterogeneous; no consistent presumably specific abnormality was detected. Nevertheless, two main patterns of nonrandom abnormalities were observed: 1) loss of chromosomes 4 and 22, 9p, and 3p in the most of the abnormal cases and corresponding to a hypodiploid and/or hypotetraploid modal chromosome number; and 2) gain of chromosomes 7, 5, and 20 with deletion or rearrangement of 3p as well in the hyperdiploid cases, which were a minority in our series. These findings are discussed in view of other reported cytogenetic studies of MM, asbestos exposure, and possible mechanisms of malignant transformation.

In plain English

This study examined chromosomes in pleural fluid cells, and in some cases tumor samples, from 40 untreated patients with confirmed malignant mesothelioma from the Rotterdam and Vlissingen area, the Netherlands: 36 men aged 44 to 83 and four women aged 72 to 83. The tumor was in the pleura (the lining around the lungs) in all but one, who had it in the pericardium. Asbestos exposure history was positive in 35, unknown in three and probably negative in two women. Analysis failed in one case. Nine cases showed normal chromosomes, which the authors interpreted as coming from non-tumor cells. The other 30 showed complex, varied abnormalities, with no single change common to all. Frequent changes included loss of chromosomes 4 and 22 and of the short arm of chromosome 9; chromosome 3 was abnormal in 27 of the 30. No chromosome marker reliably told mesothelioma apart from lung adenocarcinoma. The chromosome groups were not linked to age, survival or tumor type. The authors suggested that loss of tumor-suppressing genes on these chromosomes may play a role, but said more studies were needed.

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: Cytogenetic (chromosome) analysis of a series of malignant mesothelioma cases, with nonmalignant and metastatic carcinoma pleural effusions analyzed for comparison
• Who was studied: 40 patients with newly diagnosed, untreated, confirmed malignant mesothelioma (36 men aged 44 to 83, four women aged 72 to 83), drawn from 71 patients whose samples were received and referred from hospitals in the Rotterdam and Vlissingen area, the Netherlands. In most cases pleural effusion cells were studied, and in some cases tumor biopsy or autopsy material. Primary site was the pleura in all but one patient (pericardium). Comparison samples were 14 nonmalignant pleural effusions and 10 effusions from metastatic carcinomas. Study dates were not given.
• Exposure: History of asbestos exposure, graded from job history: high exposure (insulation, shipbuilding, demolition, cement factory, direct handling of asbestos), worker in a potentially exposed environment, no known exposure, or no data. The study did not analyze fiber types.
• Main results:
  • Asbestos exposure history was positive in 35 of the 40 patients (unknown in three, probably negative in two female patients).
  • Chromosome analysis succeeded in 39 of the 40 cases and failed in one.
  • Nine patients showed a normal karyotype (normal chromosome pattern) in pleural effusion cells.
  • 30 cases had clonal chromosome abnormalities: hypodiploid (13 cases), hypotetraploid (11 cases) and hyperdiploid (six cases).
  • No specific change common to all abnormal cases was found.
  • In the hypodiploid and hypotetraploid cases, chromosome 4 was lost 16 times and chromosome 22 was lost 15 times.
  • Chromosome 3 abnormalities were seen in 27 (90%) of the 30 abnormal karyotypes.
  • Loss of the short arm of chromosome 9 was the most consistent feature of the hypodiploid and hypotetraploid cases. Only one of these 24 cases showed no alteration of chromosome 9.
  • In the six hyperdiploid cases, chromosomes 7 and 20 were gained.
  • The chromosome groups were not correlated with age at onset, primary site, survival time or histological type.
  • In the 14 nonmalignant pleural effusions, 287 metaphases were analyzed and mostly showed a normal karyotype.
  • No chromosome marker was found that safely distinguished lung adenocarcinoma from malignant mesothelioma.
  • Among the 40 mesothelioma patients, 73% died within 1 year of diagnosis and 34% within 6 months.
• The authors' conclusion: The authors concluded that the repeated losses of 9p, 3p and chromosomes 4 and 22 suggest that loss of suppressor genes on these chromosomes may play a role in the development of mesothelioma, but said more studies are needed to establish this.
• Limitations the authors state:
  • The authors interpreted the nine normal karyotypes as probably coming from non-tumor cells (reactive mesothelial cells, inflammatory cells, contaminating fibroblasts), not from the tumors.
  • The quality of the dividing cells examined was irregular, and not all cells could be fully analyzed.
  • The authors noted that three cases classed as hypotetraploid may have been misclassified and should possibly have been counted as hyperdiploid.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleural Effusion, Biopsy, Ascites, Asbestos Exposure, Malignant Transformation.

Related studies

• Cytogenetic findings in an effusion secondary from pleural mesothelioma — M.J. Bello, J.A. Rey, et al. (1987)
• Interphase cytogenetics on paraffin sections of malignant pleural mesothelioma. A comparison to conventional karyotyping and flow cytometric studies — M. Tiainen, A. Hopman, et al. (1992)
• Abnormalities of chromosomes 7 and 22 in human malignant pleural mesothelioma: correlation between Southern blot and cytogenetic analyses — M. Tiainen, J. Kere, et al. (1992)
• Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors — K. Pelin, A. Hirvonen, et al. (1995)
• The effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting — M.J. Ramsey, D.H. Moore, et al. (1995)
• Cytogenetic studies on chrysotile asbestos — K.S. Lavappa, M.M. Fu, et al. (1975)

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