PURPOSE: To identify novel genomic regions of interest in acute myeloid leukemia (AML) with complex karyotypes, we applied comparative genomic hybridization to microarrays (array-CGH), allowing high-resolution genome-wide screening of genomic imbalances. PATIENTS AND METHODS: Sixty AML cases with complex karyotypes were analyzed using array-CGH; parallel analysis of gene expression was performed in a subset of cases. RESULTS: Genomic losses were found more frequently than gains. The most frequent losses affected 5q (77%), 17p (55%), and 7q (45%), and the most frequent genomic gains 11q (40%) and 8q (38%). Critical segments could be delineated to genomic fragments of only 0.8 to a few megabase-pairs of DNA. In lost/gained regions, gene expression profiling detected a gene dosage effect with significant lower/higher average gene expression levels across the genes located in the respective regions. Furthermore, high-level DNA amplifications were identified in several regions: 11q23.3-q24.1 (n = 7), 21q22 (n = 6), 11q23.3 (n = 5), 13q12 (n = 3), 8q24 (n = 3), 9p24 (n = 2), 12p13 (n = 2), and 20q11 (n = 2). Parallel analysis of gene expression in critical amplicons displayed overexpressed candidate genes (eg, C8FW and MYC in 8q24). CONCLUSION: In conclusion, a large spectrum of genomic imbalances, including novel recurring changes in AML with complex karyotypes, was identified using array-CGH. In addition, the combined analysis of array-CGH data with gene expression profiles allowed the detection of candidate genes involved in the pathogenesis of AML.
PURPOSE: To identify novel genomic regions of interest in acute myeloid leukemia (AML) with complex karyotypes, we applied comparative genomic hybridization to microarrays (array-CGH), allowing high-resolution genome-wide screening of genomic imbalances. PATIENTS AND METHODS: Sixty AML cases with complex karyotypes were analyzed using array-CGH; parallel analysis of gene expression was performed in a subset of cases. RESULTS: Genomic losses were found more frequently than gains. The most frequent losses affected 5q (77%), 17p (55%), and 7q (45%), and the most frequent genomic gains 11q (40%) and 8q (38%). Critical segments could be delineated to genomic fragments of only 0.8 to a few megabase-pairs of DNA. In lost/gained regions, gene expression profiling detected a gene dosage effect with significant lower/higher average gene expression levels across the genes located in the respective regions. Furthermore, high-level DNA amplifications were identified in several regions: 11q23.3-q24.1 (n = 7), 21q22 (n = 6), 11q23.3 (n = 5), 13q12 (n = 3), 8q24 (n = 3), 9p24 (n = 2), 12p13 (n = 2), and 20q11 (n = 2). Parallel analysis of gene expression in critical amplicons displayed overexpressed candidate genes (eg, C8FW and MYC in 8q24). CONCLUSION: In conclusion, a large spectrum of genomic imbalances, including novel recurring changes in AML with complex karyotypes, was identified using array-CGH. In addition, the combined analysis of array-CGH data with gene expression profiles allowed the detection of candidate genes involved in the pathogenesis of AML.
Authors: Brian Parkin; Peter Ouillette; Yin Wang; Yan Liu; Whitney Wright; Diane Roulston; Anjali Purkayastha; Amanda Dressel; Judith Karp; Paula Bockenstedt; Ammar Al-Zoubi; Moshe Talpaz; Lisa Kujawski; Yang Liu; Kerby Shedden; Sajid Shakhan; Cheng Li; Harry Erba; Sami N Malek Journal: Clin Cancer Res Date: 2010-05-26 Impact factor: 12.531
Authors: Fernando P G Silva; Inês Almeida; Bruno Morolli; Geeske Brouwer-Mandema; Hans Wessels; Rolf Vossen; Harry Vrieling; Erik W A Marijt; Peter J M Valk; Hanneke C Kluin-Nelemans; Wolfgang R Sperr; Wolf-Dieter Ludwig; Micheline Giphart-Gassler Journal: Haematologica Date: 2009-09-22 Impact factor: 9.941
Authors: Timothy J Ley; Elaine R Mardis; Li Ding; Bob Fulton; Michael D McLellan; Ken Chen; David Dooling; Brian H Dunford-Shore; Sean McGrath; Matthew Hickenbotham; Lisa Cook; Rachel Abbott; David E Larson; Dan C Koboldt; Craig Pohl; Scott Smith; Amy Hawkins; Scott Abbott; Devin Locke; Ladeana W Hillier; Tracie Miner; Lucinda Fulton; Vincent Magrini; Todd Wylie; Jarret Glasscock; Joshua Conyers; Nathan Sander; Xiaoqi Shi; John R Osborne; Patrick Minx; David Gordon; Asif Chinwalla; Yu Zhao; Rhonda E Ries; Jacqueline E Payton; Peter Westervelt; Michael H Tomasson; Mark Watson; Jack Baty; Jennifer Ivanovich; Sharon Heath; William D Shannon; Rakesh Nagarajan; Matthew J Walter; Daniel C Link; Timothy A Graubert; John F DiPersio; Richard K Wilson Journal: Nature Date: 2008-11-06 Impact factor: 49.962