TY - JOUR
T1 - Telomere maintenance in wilms tumors
T2 - First evidence for the presence of alternative lengthening of telomeres mechanism
AU - Venturini, Lorenza
AU - Daidone, Maria Grazia
AU - Motta, Rosita
AU - Collini, Paola
AU - Spreafico, Filippo
AU - Terenziani, Monica
AU - Piva, Luigi
AU - Radice, Paolo
AU - Perotti, Daniela
AU - Zaffaroni, Nadia
PY - 2011/10
Y1 - 2011/10
N2 - Unlimited proliferative potential is a hallmark of cancer, and can be achieved through the activation of telomere maintenance mechanisms (TMMs). Most tumors activate telomerase, but a significant minority, mainly of mesenchymal origin, uses a recombination-based, alternative lengthening of telomeres (ALT) mechanism. We investigated the presence of ALT in 34 Wilms tumor (WT) samples from 30 patients by using two approaches: (i) the detection of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization and (ii) the assessment of terminal restriction fragment (TRF) length distribution by pulsed field gel electrophoresis. In parallel, telomerase activity (TA) was determined by the telomeric repeat amplification protocol (TRAP) assay. Based on APB expression, ALT was detectable in five samples as the sole TMM and in six samples in association with telomerase. Seventeen samples only expressed TA and in six cases no known TMM was appreciable. Results of TRF length distribution were available in 32 cases, and a concordance between APB and TRF data in defining the ALT phenotype was found in 26/32 cases (81%). The study provides the first evidence of the presence of ALT in WT, and indicates that in a small but defined fraction of cases (about 15%) ALT is the only TMM that supports the development of WT.
AB - Unlimited proliferative potential is a hallmark of cancer, and can be achieved through the activation of telomere maintenance mechanisms (TMMs). Most tumors activate telomerase, but a significant minority, mainly of mesenchymal origin, uses a recombination-based, alternative lengthening of telomeres (ALT) mechanism. We investigated the presence of ALT in 34 Wilms tumor (WT) samples from 30 patients by using two approaches: (i) the detection of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization and (ii) the assessment of terminal restriction fragment (TRF) length distribution by pulsed field gel electrophoresis. In parallel, telomerase activity (TA) was determined by the telomeric repeat amplification protocol (TRAP) assay. Based on APB expression, ALT was detectable in five samples as the sole TMM and in six samples in association with telomerase. Seventeen samples only expressed TA and in six cases no known TMM was appreciable. Results of TRF length distribution were available in 32 cases, and a concordance between APB and TRF data in defining the ALT phenotype was found in 26/32 cases (81%). The study provides the first evidence of the presence of ALT in WT, and indicates that in a small but defined fraction of cases (about 15%) ALT is the only TMM that supports the development of WT.
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U2 - 10.1002/gcc.20903
DO - 10.1002/gcc.20903
M3 - Article
C2 - 21769957
AN - SCOPUS:80051560666
VL - 50
SP - 823
EP - 829
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
SN - 1045-2257
IS - 10
ER -