Genomics

Dataset Information

32

Adult and adolescent acute lymphoblastic leukemia


ABSTRACT: We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). 500K single nucleotide polymorphism (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. This SNP array study is the first to specifically address adult and adolescent ALL, and the resolution level 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 between different clinical, morphological, and cytogenetic subgroups. Keywords: Genomic analysis of acute lymphoblastic leukemia samples Overall design: Diagnostic samples from 45 adult or adolescent acute lymphoblastic leukemia samples were analyzed with the Affymetrix 250K Nsp, 250K Sty, and 10K 2.0 SNP arrays. Ten samples from leukemia patients in remission were used as normal controls. Copy number changes were analyzed with the NSP and STY arrays, and regions of uniparental disomies with the 10K arrays.

INSTRUMENT(S): [Mapping10K_Xba142] Affymetrix Human Mapping 10K 2.0 Array

SUBMITTER: Kajsa Paulsson  

PROVIDER: GSE9611 | GEO | 2008-04-10

SECONDARY ACCESSION(S): PRJNA103463

REPOSITORIES: GEO

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Publications

Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease.

Paulsson Kajsa K   Cazier Jean-Baptiste JB   Macdougall Finlay F   Stevens Jane J   Stasevich Irina I   Vrcelj Nikoletta N   Chaplin Tracy T   Lillington Debra M DM   Lister T Andrew TA   Young Bryan D BD  

Proceedings of the National Academy of Sciences of the United States of America 20080505 18


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  ...[more]

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