CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all — Oak Academic Publishing
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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
Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, USA
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 abnor malities associated with a given prognosis there in 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 balan ced 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 tran slocations defining BCR/ABL 1 (x4), ETV 6 /RUNX 1 (x3), and MLL/AFF 1 (x2) breakpoints with high re solution. 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.
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