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Telomere maintenance in wilms tumors: First evidence for the presence of alternative lengthening of telomeres mechanism
Author(s) -
Venturini Lorenza,
Daidone Maria Grazia,
Motta Rosita,
Collini Paola,
Spreafico Filippo,
Terenziani Monica,
Piva Luigi,
Radice Paolo,
Perotti Daniela,
Zaffaroni Nadia
Publication year - 2011
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20903
Subject(s) - telomere , telomerase , biology , microbiology and biotechnology , concordance , wilms' tumor , phenotype , cancer , cancer research , dna , genetics , gene
Abstract 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. © 2011 Wiley‐Liss, Inc.