TY - JOUR
T1 - Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia
T2 - Unexpected similarities with pediatric disease
AU - Paulsson, Kajsa
AU - Cazier, Jean-Baptiste
AU - Macdougall, Finlay
AU - Stevens, Jane
AU - Stasevich, Irina
AU - Vrcelj, Nikoletta
AU - Chaplin, Tracy
AU - Lillington, Debra M
AU - Lister, T Andrew
AU - Young, Bryan D
PY - 2008/5/6
Y1 - 2008/5/6
N2 - We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). A 500K SNP array analysis uncovered frequent genetic abnormalities, with cryptic deletions constituting half of the detected changes, implying that microdeletions are a characteristic feature of this malignancy. Importantly, the pattern of deletions resembled that recently reported in pediatric ALL, suggesting that adult, adolescent, and childhood cases may be more similar on the genetic level than previously thought. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes. Furthermore, several genes not previously implicated in the pathogenesis of ALL were identified as possible recurrent targets of deletion. In total, the SNP array analysis identified 367 genetic abnormalities not corresponding to known copy number polymorphisms, with all but two cases (96%) displaying at least one cryptic change. The resolution level of this SNP array study is the highest used to date to investigate a malignant hematologic disorder. Our findings provide insights into the leukemogenic process and may be clinically important in adult and adolescent ALL. Most importantly, we report that microdeletions of key genes appear to be a common, characteristic feature of ALL that is shared among different clinical, morphological, and cytogenetic subgroups.
AB - We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). A 500K SNP array analysis uncovered frequent genetic abnormalities, with cryptic deletions constituting half of the detected changes, implying that microdeletions are a characteristic feature of this malignancy. Importantly, the pattern of deletions resembled that recently reported in pediatric ALL, suggesting that adult, adolescent, and childhood cases may be more similar on the genetic level than previously thought. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes. Furthermore, several genes not previously implicated in the pathogenesis of ALL were identified as possible recurrent targets of deletion. In total, the SNP array analysis identified 367 genetic abnormalities not corresponding to known copy number polymorphisms, with all but two cases (96%) displaying at least one cryptic change. The resolution level of this SNP array study is the highest used to date to investigate a malignant hematologic disorder. Our findings provide insights into the leukemogenic process and may be clinically important in adult and adolescent ALL. Most importantly, we report that microdeletions of key genes appear to be a common, characteristic feature of ALL that is shared among different clinical, morphological, and cytogenetic subgroups.
KW - Adolescent
KW - Adult
KW - Aged
KW - B-Lymphocytes
KW - Cell Cycle
KW - Child
KW - Chromosome Aberrations
KW - Gene Deletion
KW - Genes, Neoplasm
KW - Genome, Human
KW - Humans
KW - Lymphopoiesis
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
U2 - 10.1073/pnas.0800408105
DO - 10.1073/pnas.0800408105
M3 - Article
C2 - 18458336
SN - 1091-6490
VL - 105
SP - 6708
EP - 6713
JO - National Academy of Sciences. Proceedings
JF - National Academy of Sciences. Proceedings
IS - 18
ER -