Author(s)

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.

Acute Lymphoblastic Leukemia; B-Cell ALL; Microarray; Balanced Translocation; Translocation CGH; Hematologic Malignancies

Schultz, R. , Tsuchiya, K. , Furrow, A. , Slovak, M. , McDaniel, L. , Wall, M. , Crawford, E. , Ning, Y. , Saleki, R. , Fang, M. , Cawich, V. , Johnson, C. , Minier, S. , Neill, N. , Morton, S. , Byerly, S. , Surti, U. , Brown, T. , Ballif, B. and Shaffer, L. (2013) CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all. Health, 5, 23-40. doi: 10.4236/health.2013.55A004.