Telomere maintenance in wilms tumors: First evidence for the presence of alternative lengthening of telomeres mechanism

Authors

  • Lorenza Venturini,

    1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Maria Grazia Daidone,

    1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Rosita Motta,

    1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Paola Collini,

    1. Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Filippo Spreafico,

    1. Pediatric Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Monica Terenziani,

    1. Pediatric Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Luigi Piva,

    1. Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author
  • Paolo Radice,

    1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    2. Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    3. IFOM Fondazione Istituto FIRC di Oncologia Molecolare
    Search for more papers by this author
  • Daniela Perotti,

    Corresponding author
    1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    2. Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy
    Search for more papers by this author
    • D. Perotti and N. Zaffaroni contributed equally to this work.

  • Nadia Zaffaroni

    1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    Search for more papers by this author

  • Supported by: Italian Association for Cancer Research (AIRC), Associazione Bianca Garavaglia, Busto Arsizio (VA), Italy, Italian Foundation for Cancer Research (FIRC).

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.

Ancillary