title: Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of childhood acute lymphoblastic leukaemia: detailed analysis of 70 cases.
abstract: Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7-15 copies) of AML1. Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL.
authors.affiliation: Department of Molecular Medicine, Karolinska Institutet, L8-02 Karolinska Hospital, SE-17176 Stockholm, Sweden. ann.nordgren@cmm.ki.se
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.forename: Sigrid
authors.initials: S
authors.lastname: Sahlén
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schoumans
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderhäll
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
mesh_terms: D000293:Adolescent; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D016313:Genes, abl; D019942:Genes, p16; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D007399:Interphase; D007621:Karyotyping / Q000379:methods*; D015458:Leukemia, T-Cell / Q000235:genetics; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010677:Philadelphia Chromosome; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic / 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