Spectral karyotyping of sarcomas and fibroblasts derived from Ink4a/Arf-deficient mice reveals chromosomal instability in vitro

Robertson,Scott A.; Schoumans,Jacqueline; Looyenga,Brendan D.; Yuhas,Jason A.; Zylstra,Cassandra R.; Koeman,Julie M.; Swiatek,Pamela J.; Teh,Bin T.; Williams,Bart O.

doi:10.3892/ijo.26.3.629

March 2005 Volume 26 Issue 3

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March 2005 Volume 26 Issue 3

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Article

Spectral karyotyping of sarcomas and fibroblasts derived from Ink4a/Arf-deficient mice reveals chromosomal instability in vitro

Authors:
- Scott A. Robertson
- Jacqueline Schoumans
- Brendan D. Looyenga
- Jason A. Yuhas
- Cassandra R. Zylstra
- Julie M. Koeman
- Pamela J. Swiatek
- Bin T. Teh
- Bart O. Williams
View Affiliations / Copyright

Affiliations: Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, MI 49503, USA
Pages: 629-634
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Published online on: March 1, 2005

https://doi.org/10.3892/ijo.26.3.629
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Abstract

The Ink4a/Arf locus is functionally linked to the Rb and p53 pathways through the action of its two gene products. Mouse models null for this locus show rapid onset of cancer with a preponderance of lymphomas and sarcomas. We report on a study of cell lines derived from sarcomas arising in Ink4a/Arf null mice. The cytogenetics of these lines was monitored over the course of serial passage. Results indicate that early passage cells are relatively normal. However, after multiple passages chromosomal instability becomes apparent as evidenced by increasing tetraploidy and aneuploidy, and the concomitant loss of clonality. To further evaluate the effect of Ink4a/Arf-deficiency on chromosomal stability in vitro, we isolated Ink4a/Arf deficient primary murine embryonic fibroblasts (MEFs), serially passaged them, and analyzed their chromosomal stability by spectral karyotyping (a 24-color chromosome paint-FISH technique). We found that chromosomal instability in Ink4a/Arf deficient MEFs developed with the same timing as seen in cell lines derived from Ink4a/Arf deficient sarcomas. Thus, chromosomal instability seen in Ink4a/Arf deficient tumors in vitro may be unrelated to the original phenotype of the tumor in vivo. Therefore, interpretation of cytogenetic data from cell lines derived from Ink4a/Arf deficient tumors should be done on early passage cells.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Spectral karyotyping of sarcomas and fibroblasts derived from Ink4a/Arf-deficient mice reveals chromosomal instability in vitro

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