TITLE:
CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all
AUTHORS:
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
KEYWORDS:
Acute Lymphoblastic Leukemia; B-Cell ALL; Microarray; Balanced Translocation; Translocation CGH; Hematologic Malignancies
JOURNAL NAME:
Health,
Vol.5 No.5A,
May
27,
2013
ABSTRACT: 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.