title: Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study.
abstract: Summary Interphase fluorescence in situ hybridization (iFISH) was used independently to reveal chromosomal abnormalities of prognostic importance in a large, consecutive series of children (n = 2367) with acute lymphoblastic leukaemia (ALL). The fusions, TEL/AML1 and BCR/ABL, and rearrangements of the MLL gene occurred at frequencies of 22% (n = 447/2027) (25% in B-lineage ALL), 2% (n = 43/2027) and 2% (n = 47/2016) respectively. There was considerable variation in iFISH signal patterns both between and within patient samples. The TEL/AML1 probe showed the highest incidence of variation (59%, n = 524/884), which included 38 (2%) patients with clustered, multiple copies of AML1. We were thus able to define amplification of AML1 as a new recurrent abnormality in ALL, associated with a poor prognosis. Amplification involving the ABL gene, a rare recurrent abnormality confined to T ALL patients, was identified for the first time. The use of centromeric probes revealed significant hidden high hyperdiploidy of 33% and 59%, respectively, in patients with normal (n = 21/64) or failed (n = 32/54) cytogenetic results. The iFISH contributed significantly to the high success rate of 91% (n = 2114/2323) and the remarkable abnormality detection rate of 89% (n = 1879/2114). This study highlights the importance of iFISH as a complementary tool to cytogenetics in routine screening for significant chromosomal abnormalities in ALL.
authors.affiliation: Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, General Hospital, Southampton SO16 6YD, UK. harrison@soton.ac.uk
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Barber
authors.forename: Zoë J
authors.initials: ZJ
authors.lastname: Broadfield
authors.forename: Kan L
authors.initials: KL
authors.lastname: Cheung
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Harris
authors.forename: G Reza
authors.initials: GR
authors.lastname: Jalali
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Robinson
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Strefford
authors.forename: Adam
authors.initials: A
authors.lastname: Stewart
authors.forename: Sarah
authors.initials: S
authors.lastname: Wright
authors.forename: Mike
authors.initials: M
authors.lastname: Griffiths
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
authors.forename: Louise
authors.initials: L
authors.lastname: Harewood
authors.forename: Mary
authors.initials: M
authors.lastname: Martineau
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005784:Gene Amplification; D015321:Gene Rearrangement; D016313:Genes, abl; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007399:Interphase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D016044:Fusion Proteins, bcr-abl; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; C497422:KMT2A protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein