No conflicts of interest were declared.
The alternative lengthening of telomeres pathway may operate in non-neoplastic human cells†
Article first published online: 4 JAN 2012
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 226, Issue 3, pages 509–518, February 2012
How to Cite
Slatter, T. L., Tan, X., Yuen, Y. C., Gunningham, S., Ma, S. S., Daly, E., Packer, S., Devenish, C., Royds, J. A. and Hung, N. A. (2012), The alternative lengthening of telomeres pathway may operate in non-neoplastic human cells. J. Pathol., 226: 509–518. doi: 10.1002/path.2981
- Issue published online: 16 JAN 2012
- Article first published online: 4 JAN 2012
- Accepted manuscript online: 12 AUG 2011 03:57AM EST
- Manuscript Accepted: 4 AUG 2011
- Manuscript Revised: 27 JUL 2011
- Manuscript Received: 8 NOV 2010
- telomere maintenance;
- alternative lengthening;
- nuclear bodies;
- non-neoplastic cells
The alternative lengthening of telomeres (ALT) mechanism represents an alternative to the enzyme telomerase in the maintenance of mammalian telomeres in 25–60% of sarcomas and a minority of carcinomas (about 5–15%). ALT-positive cells are distinguished by long and heterogeneous telomere length distributions by terminal restriction fragment (TRF) Southern blotting. Another diagnostic marker of ALT is discrete nuclear co-localized signals of telomeric DNA and the promyelocytic leukaemia protein (PML), referred to as ALT-associated PML bodies (APBs). Recently, we detected smaller sized co-localized PML and telomere DNA (APB-like) bodies in endothelial cells adjacent to astrocytoma tumour cells in situ. In this study, we examined a wide variety of non-neoplastic tissues, and report that co-localized signals of PML and telomere DNA are present in endothelial, stromal, and some epithelial cells. Co-localized signals of PML and telomere DNA showed an increased frequency in non-neoplastic cells with DNA damage. These results suggest that a mechanism similar to that in ALT-positive tumours also operates in non-neoplastic cells, which may be activated by DNA damage. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.