Tags

Type your tag names separated by a space and hit enter

Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres.
Am J Pathol 2010; 177(6):2694-700AJ

Abstract

Telomere maintenance by either telomerase activity or the recombination-mediated alternative lengthening of telomeres (ALT) mechanism is a hallmark of cancer. Tumors that use ALT as their telomere maintenance mechanism are characterized by long telomeres of great heterogeneity in length and by specific nuclear structures of co-localized promyelocytic leukemia protein and telomere DNA, called ALT-associated promyelocytic leukemia bodies (APBs). Recent advances have revealed a direct role for APBs in telomere recombination in ALT-positive cells. In this study, we investigated the possibility that APBs could occur before the long 'alternatively' lengthened telomeres arise, particularly in low-grade tumors. We measured APBs, telomere length, and telomerase activity in 64 astrocytomas inclusive of grade 1-4 tumors. Almost all grade 1-3 tumors (93%) were APB-positive using published criteria. Grade 2-3 APB-positive tumors also had long telomeres and were confirmed as ALT positive. However, grade 1 tumors lacked long telomeres and were therefore classified as ALT negative, but positive for telomere-associated promyelocytic leukemia bodies (TPB). This is the first report of a TPB-positive but ALT-negative tumor, and suggests that low-grade tumors have the foundation for recombinational telomere repair, as in ALT. Further work is warranted to characterize the TPB-positive phenotype in other early malignancies, as well as to determine whether TPBs predispose to telomere maintenance by ALT.

Authors+Show Affiliations

Department of Pathology, Dunedin School of Medicine, PO Box 913, University of Otago, Dunedin, New Zealand.No 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

21037079

Citation

Slatter, Tania, et al. "Pilocytic Astrocytomas Have Telomere-associated Promyelocytic Leukemia Bodies Without Alternatively Lengthened Telomeres." The American Journal of Pathology, vol. 177, no. 6, 2010, pp. 2694-700.
Slatter T, Gifford-Garner J, Wiles A, et al. Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres. Am J Pathol. 2010;177(6):2694-700.
Slatter, T., Gifford-Garner, J., Wiles, A., Tan, X., Chen, Y. J., MacFarlane, M., ... Hung, N. (2010). Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres. The American Journal of Pathology, 177(6), pp. 2694-700. doi:10.2353/ajpath.2010.100468.
Slatter T, et al. Pilocytic Astrocytomas Have Telomere-associated Promyelocytic Leukemia Bodies Without Alternatively Lengthened Telomeres. Am J Pathol. 2010;177(6):2694-700. PubMed PMID: 21037079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres. AU - Slatter,Tania, AU - Gifford-Garner,Jennifer, AU - Wiles,Anna, AU - Tan,Xin, AU - Chen,Yu-Jen, AU - MacFarlane,Martin, AU - Sullivan,Michael, AU - Royds,Janice, AU - Hung,Noelyn, Y1 - 2010/10/29/ PY - 2010/11/2/entrez PY - 2010/11/3/pubmed PY - 2011/3/16/medline SP - 2694 EP - 700 JF - The American journal of pathology JO - Am. J. Pathol. VL - 177 IS - 6 N2 - Telomere maintenance by either telomerase activity or the recombination-mediated alternative lengthening of telomeres (ALT) mechanism is a hallmark of cancer. Tumors that use ALT as their telomere maintenance mechanism are characterized by long telomeres of great heterogeneity in length and by specific nuclear structures of co-localized promyelocytic leukemia protein and telomere DNA, called ALT-associated promyelocytic leukemia bodies (APBs). Recent advances have revealed a direct role for APBs in telomere recombination in ALT-positive cells. In this study, we investigated the possibility that APBs could occur before the long 'alternatively' lengthened telomeres arise, particularly in low-grade tumors. We measured APBs, telomere length, and telomerase activity in 64 astrocytomas inclusive of grade 1-4 tumors. Almost all grade 1-3 tumors (93%) were APB-positive using published criteria. Grade 2-3 APB-positive tumors also had long telomeres and were confirmed as ALT positive. However, grade 1 tumors lacked long telomeres and were therefore classified as ALT negative, but positive for telomere-associated promyelocytic leukemia bodies (TPB). This is the first report of a TPB-positive but ALT-negative tumor, and suggests that low-grade tumors have the foundation for recombinational telomere repair, as in ALT. Further work is warranted to characterize the TPB-positive phenotype in other early malignancies, as well as to determine whether TPBs predispose to telomere maintenance by ALT. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/21037079/Pilocytic_astrocytomas_have_telomere_associated_promyelocytic_leukemia_bodies_without_alternatively_lengthened_telomeres_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)62897-0 DB - PRIME DP - Unbound Medicine ER -