The alternative lengthening of telomeres pathway may operate in non-neoplastic human cells

• Published in: The Journal of pathology Vol. 226; no. 3; pp. 509 - 518
• Main Authors: Slatter, Tania L, Tan, Xin, Yuen, Yi Ching, Gunningham, Sarah, Ma, Sally SiYan, Daly, Erin, Packer, Stephen, Devenish, Celia, Royds, Janice A, Hung, Noelyn A
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-02-2012; Wiley
• Subjects: Adult; Aged; Aged, 80 and over; alternative lengthening; Biological and medical sciences; Case-Control Studies; Cells, Cultured; DNA - analysis; Endothelial Cells - pathology; Epithelial Cells - pathology; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Middle Aged; Neoplasms - pathology; non-neoplastic cells; nuclear bodies; Nuclear Proteins - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Promyelocytic Leukemia Protein; Stromal Cells - pathology; Telomere - genetics; Telomere - pathology; Telomere Homeostasis - physiology; telomere maintenance; Transcription Factors - metabolism; Tumor Suppressor Proteins - metabolism; Young Adult; Human; Anatomic pathology; nuclear bodies; non-neoplastic cells; alternative lengthening; telomere maintenance; Malignant tumor; Alternative lengthening of telomeres; Cell; Body; Telomere; Cancer
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2981

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.