title: The alternative lengthening of telomeres pathway may operate in non-neoplastic human cells.
abstract: 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.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, Health Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Tania L
authors.initials: TL
authors.lastname: Slatter
authors.forename: Xin
authors.initials: X
authors.lastname: Tan
authors.forename: Yi Ching
authors.initials: YC
authors.lastname: Yuen
authors.forename: Sarah
authors.initials: S
authors.lastname: Gunningham
authors.forename: Sally Siyan
authors.initials: SS
authors.lastname: Ma
authors.forename: Erin
authors.initials: E
authors.lastname: Daly
authors.forename: Stephen
authors.initials: S
authors.lastname: Packer
authors.forename: Celia
authors.initials: C
authors.lastname: Devenish
authors.forename: Janice A
authors.initials: JA
authors.lastname: Royds
authors.forename: Noelyn A
authors.initials: NA
authors.lastname: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D042783:Endothelial Cells / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D017154:Stromal Cells / Q000473:pathology*; D016615:Telomere / Q000235:genetics / Q000473:pathology*; D059505:Telomere Homeostasis / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D004247:DNA