title: Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric acute lymphoblastic leukemia.
abstract: BACKGROUND
  Differences in survival have been reported between pediatric and adult acute lymphoblastic leukemia. The inferior prognosis in adult acute lymphoblastic leukemia is not fully understood but could be attributed, in part, to differences in genomic alterations found in adult as compared to in pediatric acute lymphoblastic leukemia.
  
  
  METHODS
  We compared two different sets of high-density single nucleotide polymorphism array genotyping data from 75 new diagnostic adult and 399 previously published diagnostic pediatric acute lymphoblastic leukemia samples. The patients' samples were randomly acquired from among Caucasian and Asian populations and hybridized to either Affymetrix 50K or 250K single nucleotide polymorphism arrays. The array data were investigated with Copy Number Analysis for GeneChips (CNAG) software for allele-specific copy number analysis.
  
  
  RESULTS
  The high density single nucleotide polymorphism array analysis of 75 samples of adult acute lymphoblastic leukemia led to the identification of numerous cryptic and submicroscopic genomic lesions with a mean of 7.6 genomic alterations per sample. The patterns and frequencies of lesions detected in the adult samples largely reproduced known genomic hallmarks detected in previous single nucleotide polymorphism-array studies of pediatric acute lymphoblastic leukemia, such as common deletions of 3p14.2 (FHIT), 5q33.3 (EBF), 6q, 9p21.3 (CDKN2A/B), 9p13.2 (PAX5), 13q14.2 (RB1) and 17q11.2 (NF1). Some differences between adult and pediatric acute lymphoblastic leukemia were identified when the pediatric data set was partitioned into hyperdiploid and non-hyperdiploid cases and then compared to the nearly exclusively non-hyperdiploid adult samples. In this analysis, adult samples had a higher rate of deletions of chromosome 17p (TP53) and duplication of 17q.
  
  
  CONCLUSIONS
  Our analysis of adult acute lymphoblastic leukemia cases led to the identification of new potential target lesions relevant for the pathogenesis of acute lymphoblastic leukemia. However, no unequivocal pattern of submicroscopic genomic alterations was found to separate adult acute lymphoblastic leukemia from pediatric acute lymphoblastic leukemia. Therefore, apart from different therapy regimen, differences of prognosis between adult and pediatric acute lymphoblastic leukemia are probably based on genetic subgroups according to cytogenetically detectable lesions but not focal genomic copy number microlesions.
authors.affiliation: Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700, Beverly Blvd, Los Angeles, CA90048, USA. Ryoko.okamoto@cshs.org
authors.forename: Ryoko
authors.initials: R
authors.lastname: Okamoto
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Daniel
authors.initials: D
authors.lastname: Nowak
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kawamata
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Akagi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.forename: Tamara
authors.initials: T
authors.lastname: Weiss
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.forename: Christian
authors.initials: C
authors.lastname: Ruckert
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D017384:Sequence Deletion; D055815:Young Adult