Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Pilocytic Astrocytomas Have Telomere-Associated Promyelocytic Leukemia Bodies without Alternatively Lengthened Telomeres

Pilocytic Astrocytomas Have Telomere-Associated Promyelocytic Leukemia Bodies without... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Pathology American Society for Investigative Pathology

Pilocytic Astrocytomas Have Telomere-Associated Promyelocytic Leukemia Bodies without Alternatively Lengthened Telomeres

Pilocytic Astrocytomas Have Telomere-Associated Promyelocytic Leukemia Bodies without Alternatively Lengthened Telomeres

American Journal of Pathology , Volume 177 (6): 2694 – Dec 1, 2010

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.

Loading next page...
 
/lp/american-society-for-investigative-pathology/pilocytic-astrocytomas-have-telomere-associated-promyelocytic-leukemia-DIsLzUAYno

References (48)

Publisher
American Society for Investigative Pathology
Copyright
Copyright © 2010 by the American Society for Investigative Pathology.
ISSN
0002-9440
eISSN
1525-2191
DOI
10.2353/ajpath.2010.100468
pmid
21037079
Publisher site
See Article on Publisher Site

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.

Journal

American Journal of PathologyAmerican Society for Investigative Pathology

Published: Dec 1, 2010

There are no references for this article.