[1486] FISH-Based Molecular Assay for i17q REPA/REPB Rearrangement in Medulloblastoma; a Blinded Study

GA Bien-Willner, D Lopez-Terrada, MB Bhattacharjee, K Patel, P Stankiewicz, A Perry, JR Lupski. Washington University School of Medicine, St. Louis, MO; Baylor College of Medicine, Houston, TX; Texas Children's Hospital, Houston, TX

Background: Medulloblastoma is the most common malignant brain tumor in children, accounting for 20 percent of all pediatric central nervous system tumors. Despite its relatively high incidence, the biology of this entity is poorly understood. Diagnosis is made based on morphology (histology), and prognosis is dependant on staging, tumor size, and age of onset. However, clinical factors do not accurately predict which standard-risk patients will have early relapse and die. Outcome is believed to be influenced by the presence of certain molecular markers, including N-MYC and C-MYC amplification, TrkC expression, and the presence of i17q chromosome. i17q has been shown to correlate with poor prognosis; however, data demonstrating that it is of prognostic value independently of anaplasia are lacking. Furthermore, i17q is typically identified by karotyping analysis, which necessitates the laborious process of culturing tumor cells and isolating mitotic figures. In a majority of cases, i17q is not a true isochromosome but an isodicentric chromosome (idic(17)(p11.2)), with rearrangement breakpoints within the REPA/REPB low-copy repeat element region in 17p11.2. Low-copy repeat elements are large DNA elements (larger than 1 kb) with greater than 90% homology that facilitate rearrangements by non-allelic homologous recombination.
Design: We have developed a FISH-based assay to identify rearrangements of the REPA/REPB region in formalin-fixed, paraffin-embedded tumor tissue specimens. This assay allows for the relatively rapid identification of i17q in archival specimens, as well as for the study of REPA/REPB rearrangements in medulloblastoma. We compared this novel FISH-based approach to standard karyotyping analysis in 17 archived medulloblastoma cases in a blinded fashion.
Results: Of 17 cases analyzed, the presence or absence of i17q was identified in 16 in agreement with the karyotype reports, with one false negative. Further investigation will determine the independent prognostic significance of REPA/REPB rearrangement in medulloblastoma.
Conclusions: This novel FISH-based assay provides a rapid and accurate method to detect i17q compared to karyotype analysis, and should facilitate further investigation of i17q in medulloblastoma.
Category: Neuropathology

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 217, Monday Morning