title: Loss at 12p detected by comparative genomic hybridization (CGH): association with TEL-AML1 fusion and favorable prognostic features in childhood acute lymphoblastic leukemia (ALL). A multi-institutional study.
abstract: BACKGROUND
  Genetic aberrations provide prognostic information in childhood ALL. The proportion of patients with detectable aberrations can be increased by combining G-banding with comparative genomic hybridization (CGH).
  
  
  METHODS
  We studied 79 children with ALL by CGH and G-banding, and explored the relationship of these findings to clinical features and outcome.
  
  
  RESULTS
  CGH revealed DNA copy number changes in 57 patients (72%), 9 of whom had normal karyotype by G-banding. Gains were more frequent than losses, and changes of whole chromosomes more frequent than partial aberrations. Two frequent partial losses were found; at 9p and 12p. The 9 patients with loss at 12p were studied for the deletion of TEL (ETV6) gene and the fusion of TEL and AML1 genes by fluorescent in situ hybridization (FISH). Eight out of the 9 children with loss at 12p harbored the TEL-AML1 translocation and all 9 had the deletion of a nontranslocated TEL allele. All 9 had precursor-B phenotype and L1 morphology, and 8/9 had WBC below 50 x 10(9)/liter. All children were treated according to Nordic ALL protocols, had a good response to treatment based on day 15 bone marrow morphology, and 7 out of the 9 survived in continuous complete remission (median follow-up 74 months).
  
  
  CONCLUSIONS
  CGH is a valuable tool in screening for genetic aberrations in childhood ALL. DNA copy number losses detected at 12p associate with TEL-AML1 fusion as well as with favorable prognostic features.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland. jukka.kanerva@hus.fi
authors.forename: J
authors.initials: J
authors.lastname: Kanerva
authors.forename: T
authors.initials: T
authors.lastname: Niini
authors.forename: K
authors.initials: K
authors.lastname: Vettenranta
authors.forename: P
authors.initials: P
authors.lastname: Riikonen
authors.forename: A
authors.initials: A
authors.lastname: Mäkipernaa
authors.forename: R
authors.initials: R
authors.lastname: Karhu
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
authors.forename: U M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007621:Karyotyping; D019656:Loss of Heterozygosity; D008297:Male; D009693:Nucleic Acid Hybridization; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein