title: Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease.
abstract: 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.
authors.affiliation: Cancer Research UK Medical Oncology Centre, Barts and the London School of Medicine, Queen Mary College, London EC1M 6BQ, United Kingdom. kajsa.paulsson@cancer.org.uk
authors.forename: Kajsa
authors.initials: K
authors.lastname: Paulsson
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Cazier
authors.forename: Finlay
authors.initials: F
authors.lastname: Macdougall
authors.forename: Jane
authors.initials: J
authors.lastname: Stevens
authors.forename: Irina
authors.initials: I
authors.lastname: Stasevich
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Vrcelj
authors.forename: Tracy
authors.initials: T
authors.lastname: Chaplin
authors.forename: Debra M
authors.initials: DM
authors.lastname: Lillington
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D017353:Gene Deletion; D052138:Genes, Neoplasm; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D038041:Lymphopoiesis / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*