Molecular inversion probes reveal patterns of 9p21 deletion and copy number aberrations in childhood leukemia.
Childhood leukemia, which accounts for >30% of newly diagnosed childhood malignancies, is one of the leading causes of death for children with cancer. Genome-wide studies using microarray chips to identify copy number changes in human cancer are becoming more common. In this pilot study, 45 pediatric leukemia samples were analyzed for gene copy aberrations using novel molecular inversion probe (MIP) technology. Acute leukemia subtypes included precursor B-cell acute lymphoblastic leukemia (ALL) (n=23), precursor T-cell ALL (n=6), and acute myeloid leukemia (n=14). The MIP analysis identified 69 regions of recurring copy number changes, of which 41 have not been identified with other DNA microarray platforms. Copy number gains and losses were validated in 98% of clinical karyotypes and 100% of fluorescence in situ hybridization studies available. We report unique patterns of copy number loss in samples with 9p21.3 (CDKN2A) deletion in the precursor B-cell ALL patients, compared with the precursor T-cell ALL patients. MIPs represent an attractive technology for identifying novel copy number aberrations, validating previously reported copy number changes, and translating molecular findings into clinically relevant targets for further investigation.
Schiffman
Joshua D
JD
Pediatric Hematology/Oncology and Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Room 4343, Salt Lake City, UT 84112. Joshua.Schiffman@hci.utah.edu
Wang
Yuker
Y
McPherson
Lisa A
LA
Welch
Katrina
K
Zhang
Nancy
N
Davis
Ronald
R
Lacayo
Norman J
NJ
Dahl
Gary V
GV
Faham
Malek
M
Ford
James M
JM
Ji
Hanlee P
HP
D000293:Adolescent; D002051:Burkitt Lymphoma / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D020732:Cytogenetic Analysis; D003627:Data Interpretation, Statistical; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D015336:Molecular Probe Techniques; D051757:PAX5 Transcription Factor / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D015203:Reproducibility of Results
D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human