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A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas.
Clin Cancer Res. 2005 Jan 01; 11(1):217-25.CC

Abstract

PURPOSE AND EXPERIMENTAL DESIGN

Telomeres of tumor cells may be maintained by telomerase or by alternative lengthening of telomeres (ALT). The standard ALT assay requires Southern analysis of high molecular weight genomic DNA. We aimed to establish and validate an ALT assay suitable for archived paraffin-embedded tumors and to use it to examine the prevalence and clinical significance of ALT in various types of tumors that are often telomerase negative.

RESULTS

To assay for ALT, we detected ALT-associated promyelocytic leukemia (PML) bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization. APBs are PML nuclear domains containing telomeric DNA and are a known hallmark of ALT in cell lines. The APB assay concurred with the standard ALT assay in 62 of 62 tumors and showed that 35% of 101 soft tissue sarcomas (STS), 47% of 58 osteosarcomas (especially younger patients), 34% of 50 astrocytomas, and 0% of 17 papillary thyroid carcinomas were ALT positive (ALT+). The prevalence of ALT varied greatly among different STS subtypes: malignant fibrous histiocytomas, 77%; leiomyosarcomas, 62%; liposarcomas, 33%; synovial sarcomas, 9%; and rhabdomyosarcomas, 6%. ALT correlated with survival in glioblastoma multiforme and occurred more often in lower-grade astrocytomas, but ALT+ and ALT- sarcomas were equally aggressive in terms of grade and clinical outcome.

CONCLUSION

The APB assay for ALT is suitable for paraffin-embedded tumors. It showed that a substantial proportion of STS, osteosarcomas, and astrocytomas, but not papillary thyroid carcinomas use ALT. APB positivity correlated strongly with survival of patients with astrocytomas.

Authors+Show Affiliations

Children's Medical Research Institute, New South Wales, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15671549

Citation

Henson, Jeremy D., et al. "A Robust Assay for Alternative Lengthening of Telomeres in Tumors Shows the Significance of Alternative Lengthening of Telomeres in Sarcomas and Astrocytomas." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 1, 2005, pp. 217-25.
Henson JD, Hannay JA, McCarthy SW, et al. A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas. Clin Cancer Res. 2005;11(1):217-25.
Henson, J. D., Hannay, J. A., McCarthy, S. W., Royds, J. A., Yeager, T. R., Robinson, R. A., Wharton, S. B., Jellinek, D. A., Arbuckle, S. M., Yoo, J., Robinson, B. G., Learoyd, D. L., Stalley, P. D., Bonar, S. F., Yu, D., Pollock, R. E., & Reddel, R. R. (2005). A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(1), 217-25.
Henson JD, et al. A Robust Assay for Alternative Lengthening of Telomeres in Tumors Shows the Significance of Alternative Lengthening of Telomeres in Sarcomas and Astrocytomas. Clin Cancer Res. 2005 Jan 1;11(1):217-25. PubMed PMID: 15671549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas. AU - Henson,Jeremy D, AU - Hannay,Jonathan A, AU - McCarthy,Stanley W, AU - Royds,Janice A, AU - Yeager,Thomas R, AU - Robinson,Robert A, AU - Wharton,Stephen B, AU - Jellinek,David A, AU - Arbuckle,Susan M, AU - Yoo,Jinyoung, AU - Robinson,Bruce G, AU - Learoyd,Diana L, AU - Stalley,Paul D, AU - Bonar,S Fiona, AU - Yu,Dihua, AU - Pollock,Raphael E, AU - Reddel,Roger R, PY - 2005/1/27/pubmed PY - 2005/6/29/medline PY - 2005/1/27/entrez SP - 217 EP - 25 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 11 IS - 1 N2 - PURPOSE AND EXPERIMENTAL DESIGN: Telomeres of tumor cells may be maintained by telomerase or by alternative lengthening of telomeres (ALT). The standard ALT assay requires Southern analysis of high molecular weight genomic DNA. We aimed to establish and validate an ALT assay suitable for archived paraffin-embedded tumors and to use it to examine the prevalence and clinical significance of ALT in various types of tumors that are often telomerase negative. RESULTS: To assay for ALT, we detected ALT-associated promyelocytic leukemia (PML) bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization. APBs are PML nuclear domains containing telomeric DNA and are a known hallmark of ALT in cell lines. The APB assay concurred with the standard ALT assay in 62 of 62 tumors and showed that 35% of 101 soft tissue sarcomas (STS), 47% of 58 osteosarcomas (especially younger patients), 34% of 50 astrocytomas, and 0% of 17 papillary thyroid carcinomas were ALT positive (ALT+). The prevalence of ALT varied greatly among different STS subtypes: malignant fibrous histiocytomas, 77%; leiomyosarcomas, 62%; liposarcomas, 33%; synovial sarcomas, 9%; and rhabdomyosarcomas, 6%. ALT correlated with survival in glioblastoma multiforme and occurred more often in lower-grade astrocytomas, but ALT+ and ALT- sarcomas were equally aggressive in terms of grade and clinical outcome. CONCLUSION: The APB assay for ALT is suitable for paraffin-embedded tumors. It showed that a substantial proportion of STS, osteosarcomas, and astrocytomas, but not papillary thyroid carcinomas use ALT. APB positivity correlated strongly with survival of patients with astrocytomas. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15671549/A_robust_assay_for_alternative_lengthening_of_telomeres_in_tumors_shows_the_significance_of_alternative_lengthening_of_telomeres_in_sarcomas_and_astrocytomas_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15671549 DB - PRIME DP - Unbound Medicine ER -