High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy‐neutral loss of heterozygosity and copy number alterations that target single genes |
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| Authors: | K‐John J. Cheung Allen Delaney Susana Ben‐Neriah Jacquie Schein Tang Lee Sohrab P. Shah Dorothy Cheung Nathalie A. Johnson Andrew J. Mungall Adele Telenius Betty Lai Merrill Boyle Joseph M. Connors Randy D. Gascoyne Marco A. Marra Douglas E. Horsman |
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| Affiliation: | 1. Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC;2. Genome Sciences Center, British Columbia Cancer Research Center, Vancouver, BC |
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| Abstract: | A multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, was applied to the study of the tumor genomes of 25 follicular lymphoma biopsy samples with paired normal DNA samples to characterize balanced translocations, copy number imbalances, and copy‐neutral loss of heterozygosity (cnLOH). In addition to the t(14;18), eight unique balanced translocations were found. Commonly reported FL‐associated copy number regions were revealed including losses of 1p32‐36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by copy‐neutral loss of heterozygosity were 1p36.33 (28%), 6p21.3 (20%), 12q21.2‐q24.33 (16%), and 16p13.3 (24%). We also identified by SNP analysis, 45 aberrant regions that each affected one gene, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD, which were associated with canonical pathways involved in tumor development. This study illustrates the power of using complementary high‐resolution platforms on paired tumor/normal specimens and computational analysis to provide potential insights into the significance of single‐gene somatic aberrations in FL tumorigenesis. © 2010 Wiley‐Liss,Inc. |
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