4.7 Article

Increased chromosomal stability in cultures of ovarian tumours of low malignant potential compared to cystadenomas

Journal

BRITISH JOURNAL OF CANCER
Volume 96, Issue 12, Pages 1908-1913

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6603817

Keywords

ovarian neoplasms; cellular aging; telomeres; aneuploidy; chromosomal stability

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Funding

  1. NCI NIH HHS [R01 CA119078, R01 CA079750, R01CA119078, R01CA79750] Funding Source: Medline

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Cell cultures of ovarian cystadenomas transfected with SV40 large T antigen are not immortal because they invariably reach a phenomenon called crisis, which is triggered in part by telomere attrition. Recovery from crisis may be an integral component of the malignant transformation process. We reported earlier that such ovarian cystadenoma cell cultures undergo severe changes in DNA ploidy as they approach crisis and that such changes are an important determinant of crisis independent of telomere attrition. Here, we show that in sharp contrast to these benign ovarian tumours, the DNA content of ovarian tumours of low malignant potential (LMP) was remarkably stable as they approached crisis, suggesting that telomere attrition was the main determinant of this mortality checkpoint. Lack of a ploidy-based crisis was not due to loss of expression of a functional SV40 large T antigen protein. We conclude that ovarian LMP tumours are characterised by increased numerical chromosomal stability compared to cystadenomas. This might account for the fact that most LMP tumours are diploid or near diploid in vivo. This fundamental difference in chromosomal stability between ovarian cystadenomas and LMP tumours also suggests potential differences in predisposition to progression to malignancy between these two ovarian tumour subtypes.

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