Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines

Our plain-English summary of Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines, by E. Wahlbuhl, T. Liehr, M. Rincic, et al (Molecular Cytogenetics, 2020).

The study

• Authors: E. Wahlbuhl, T. Liehr, M. Rincic, S. Azawi
• Journal: Molecular Cytogenetics
• Published: 2020;13:43
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma (MM) is a rare aggressive cancer primary located in pleura and lung. MMs can be divided into biphasic, epithelioid and sarcomatoid subtypes. In majority of cases MMs are induced by asbestos fiber exposure. As latency period after asbestos exposure ranges between ~ 10 and 60 years MMs are mainly observed in elder people. Human MM, being a rare tumor type, lacks detailed cytogenetic data, while molecular genetic studies have been undertaken more frequently. However, murine MM cell lines are also regularly applied to get more insight into MM biology and to test new therapy strategies.

Results: Here the murine MM cell lines AB1, AB22 and AC29 were studied by molecular cytogenetics and molecular karyotyping. Interestingly, yet there were no genetic or genomic studies undertaken for these already in 1992 established cell lines. The obtained data on genomic imbalances in these murine cell lines was translated into the human genome as previously reported based on human and murine genomic browsers.

Conclusions: It turned out that all three cell lines showed high similarities in copy number variants as observed typically in human MM. Also, all three cell lines were most similar to human epithelioid MMs, and should be used as models therefore.

© The Author(s) 2020.

In plain English

This laboratory study examined chromosomes and DNA in three mouse mesothelioma cell lines: AB1, AB22 and AC29. The article says other researchers established these lines in 1992 from mice inoculated with asbestos fibers. It does not name the fiber type. The authors used multicolor chromosome staining and a test for gained or lost stretches of DNA. They mapped the changes onto human genome regions and compared them with published human data. AB1 and AB22 had about four chromosome sets; AC29 had just over three. AB1 shared 14/16 (88%) changes with human epithelioid and 17/21 (81%) with human sarcomatoid mesothelioma. AC29 shared 15/20 (75%) and 15/22 (68%). For AB22 the figures conflict: the text gives 18/20 (94%) for epithelioid, though 18/20 is 90%, and 17/21 (81%) for sarcomatoid, where the table gives 21/23. All three lines were less similar to the biphasic type. The authors stated they are definitely not models for biphasic mesothelioma, and concluded they are best suited as models for human epithelioid mesothelioma. They noted the extra chromosome sets may have arisen in laboratory culture.

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: Laboratory (in vitro) cytogenetic and genomic study of mouse tumor cell lines, with the mouse findings mapped onto the human genome and compared with published human mesothelioma data
• Who was studied: Three murine (mouse) malignant mesothelioma cell lines: AB1 and AC29 obtained from Cell Bank Australia, and AB22 from the European Collection of Authenticated Cell Cultures. At least 30 metaphases (dividing cells) were analyzed per probe set.
• Exposure: This study did not study an exposure. According to the background, which cites an earlier 1992 study, the cell lines came from female BALB/c and CBA mice inoculated with asbestos fibers. No fiber type is named.
• Main results:
  • AB1 had a hypotetraploid karyotype (somewhat fewer than four chromosome sets).
  • AB22 was near tetraploid.
  • AC29 was hyper-triploid (somewhat more than three chromosome sets), with a main clone making up 90% of cells and a subclone making up 10%.
  • AB1 shared 14/16 (88%) of its translated changes with human epithelioid mesothelioma and 17/21 (81%) with human sarcomatoid mesothelioma.
  • For AB22, the article's figures are inconsistent. The text gives concordance of 18/20 (94%) with human epithelioid mesothelioma, but 18/20 is 90%. It gives 17/21 (81%) with human sarcomatoid mesothelioma, but Table 1 shows 21/23 for sarcomatoid.
  • For AC29, similarity was 15/20 (75%) with human epithelioid and 15/22 (68%) with human sarcomatoid mesothelioma.
  • All three cell lines were less similar to the human biphasic mesothelioma subtype. Table 1 shows 9/19 for AB1, 15/22 for AB22 and 10/23 for AC29.
  • The discussion states that the mouse region matching the human CDKN2A gene was deleted in AB1 and AC29 but duplicated in AB22. It also states there was less or no concordance for BAP1, NF2 and TP53.
• The authors' conclusion: The authors concluded that all three cell lines can serve as models for human epithelioid mesothelioma and may also be used for sarcomatoid mesothelioma, but are definitely not models for human biphasic mesothelioma.
• Limitations the authors state:
  • The extra chromosome sets may have arisen during cell culture rather than in the original tumors. Because no karyotypes of the original tumors or early cell passages are available, the authors say this cannot be tested.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleura, Biphasic Mesothelioma, Epithelioid, Sarcomatoid, Latency, Asbestos Exposure.

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