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CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all

引用

Health 2013年第5期5卷 23-40页

作者： Roger A. Schultz karen tsuchiya Aubry Furrow Marilyn L. Slovak Lisa D. McDaniel Meaghan Wall Eric Crawford Yi Ning Reza Saleki Min Fang Victoria Cawich Caitlin E. Johnson Sara L. Minier Nicholas J. Neill S. Annie Morton Steve Byerly Urvashi Surti Theresa C. Brown Blake C. Ballif Lisa G. Shaffer Department of Molecular and Human Genetics Baylor College of Medicine Houston USA Empire Genomics Buffalo USA Fred Hutchinson Cancer Research Center Seattle USA Genetics Associates Inc. Nashville USA Johns Hopkins University School of Medicine Baltimore USA Magee-Womens Hospital University of Pittsburgh Medical Center Pittsburgh USA Pathology Associates Medical Laboratories (PAML) Spokane USA Paw Print Genetics Genetic Veterinary Sciences Inc. Spokane USA Seattle Children’s Hospital Seattle USA Signature Genomic Laboratories PerkinElmer Inc. Spokane USA Signature Genomic Laboratories PerkinElmer Inc. Spokane USA Sonora Quest Laboratories Tempe USA Victorian Cancer Cytogenetics Service St. Vincent’s Hospital Melbourne Fitzroy Australia

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with the majority of cases being of precursor B-cell phenoltype. Conventional cytogenetic analysis plays an important role in the diagnosis of B-cell ALL, identifying characteristic chromosomal abnormalities associated with a given prognosis therein facilitating optimized treatment. The more recent introduction of microarray technology to the analysis of B-cell ALL has afforded both higher resolution for the detection of known abnormalities and an ability to identify novel copy number abnormalities (CNAs) with potential clinical relevance. In the current study, microarray analysis was performed on 20 cytogenetically abnormal B-cell ALL cases (10 pediatric and 10 adult), while a novel microarray-based balanced-translocation detection methodology (translocation CGH or tCGH) was applied to that subset of cases with a known or suspected recurrent balanced translocation. Standard microarray analysis identified that CNAs was not detected by previous conventional cytogenetics in 75% (15/20) cases. tCGH identified 9/9 (100%) balanced translocations defining BCR/ABL1 (x4), ETV6/RUNX1 (x3), and MLL/AFF1 (x2) breakpoints with high resolution. The results illustrate the improved molecular detail afforded by these technologies and a comparison of translocation breakpoints, CNAs and patient age offers new insights into tumor biology with potential prognostic significance.

关键词： Acute Lymphoblastic Leukemia B-Cell ALL Microarray Balanced Translocation Translocation CGH Hematologic Malignancies

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