title: Genetic abnormalities involved in t(12;21) TEL-AML1 acute lymphoblastic leukemia: analysis by means of array-based comparative genomic hybridization.
abstract: The TEL (ETV6)-AML1 (RUNX1) chimeric gene fusion is the most common genetic abnormality in childhood acute lymphoblastic leukemias. Evidence suggests that this chimeric gene fusion constitutes an initiating mutation that is necessary but insufficient for the development of leukemia. In a search for additional genetic events that could be linked to the development of leukemia, we applied a genome-wide array-comparative genomic hybridization technique to 24 TEL-AML1 leukemia samples and two cell lines. It was found that at least two chromosomal imbalances were involved in all samples. Recurrent regions of chromosomal imbalance (>10% of cases) and representative involved genes were gain of chromosomes 10 (17%) and 21q (25%; RUNX1) and loss of 12p13.2 (87%; TEL), 9p21.3 (29%; p16INK4a/ARF), 9p13.2 (25%; PAX5), 12q21.3 (25%; BTG1), 3p21 (21%; LIMD1), 6q21 (17%; AIM1 and BLIMP1), 4q31.23 (17%; NR3C2), 11q22-q23 (13%; ATM) and 19q13.11-q13.12 (13%; PDCD5). Enforced expression of TEL and to a lesser extent BTG1, both single genes known to be located in their respective minimum common region of loss, inhibited proliferation of the TEL-AML1 cell line Reh. Together, these findings suggest that some of the genes identified as lost by array-comparative genomic hybridization may partly account for the development of leukemia.
authors: Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors: Shinobu
authors: S
authors: Tsuzuki
authors: Sivasundaram
authors: S
authors: Karnan
authors: Keizo
authors: K
authors: Horibe
authors: Kimikazu
authors: K
authors: Matsumoto
authors: Koji
authors: K
authors: Kato
authors: Takeshi
authors: T
authors: Inukai
authors: Kumiko
authors: K
authors: Goi
authors: Kanji
authors: K
authors: Sugita
authors: Shinpei
authors: S
authors: Nakazawa
authors: Yumiko
authors: Y
authors: Kasugai
authors: Ryuzo
authors: R
authors: Ueda
authors: Masao
authors: M
authors: Seto
mesh_terms: D000293:Adolescent; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C074086:BTG1 protein, human