Pilocytic astrocytomas have telomere-associated promyelocytic leukemia bodies without alternatively lengthened telomeres.

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 con firmed 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 (Am J Pathol 2010 177 2694-2700, DOI 10 2353/ajpath 2010 100468)