title: Telomere maintenance in Wilms tumors: first evidence for the presence of alternative lengthening of telomeres mechanism.
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.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Venturini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Rosita
authors.initials: R
authors.lastname: Motta
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.forename: Luigi
authors.initials: L
authors.lastname: Piva
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D021141:Nucleic Acid Amplification Techniques; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D059505:Telomere Homeostasis; D009396:Wilms Tumor / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D019098:Telomerase