Format

Send to

Choose Destination
Cell Rep. 2017 Jun 20;19(12):2544-2556. doi: 10.1016/j.celrep.2017.05.087.

Extensive Proliferation of Human Cancer Cells with Ever-Shorter Telomeres.

Author information

1
Children's Cancer Research Unit, The Children's Hospital at Westmead, University of Sydney, Westmead, NSW 2145, Australia.
2
Telomere Length Regulation Unit, Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia.
3
Cancer Research Unit, Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia.
4
Cancer Cell Immortality Group, Adult Cancer Program, Prince of Wales Clinical School, University of New South Wales, Randwick, NSW 2052, Australia.
5
Bioinformatics Unit, Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia.
6
Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
7
Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Australia, Randwick, NSW 2031, Australia.
8
Children's Cancer Research Unit, The Children's Hospital at Westmead, University of Sydney, Westmead, NSW 2145, Australia; Cancer Research Unit, Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia.
9
Cancer Research Unit, Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia. Electronic address: rreddel@cmri.org.au.

Abstract

Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative. Here, we show that a subset of high-risk neuroblastomas (with āˆ¼50% 5-year mortality) lacked significant TLM activity. Cancer cells derived from these highly aggressive tumors initially had long telomeres andĀ proliferated for >200 population doublings with ever-shorter telomeres. This indicates that prevention of telomere shortening is not always required for oncogenesis, which has implications for inhibiting TLMs for cancer therapy.

KEYWORDS:

alternative lengthening of telomeres; ever-shorter telomeres; neuroblastoma; telomerase; telomeres

PMID:
28636942
DOI:
10.1016/j.celrep.2017.05.087
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center