Genetic abnormalities involved in t(12;21) TEL-AML1 acute lymphoblastic leukemia: analysis by means of array-based comparative genomic hybridization.
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.
Tsuzuki
Shinobu
S
Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Karnan
Sivasundaram
S
Horibe
Keizo
K
Matsumoto
Kimikazu
K
Kato
Koji
K
Inukai
Takeshi
T
Goi
Kumiko
K
Sugita
Kanji
K
Nakazawa
Shinpei
S
Kasugai
Yumiko
Y
Ueda
Ryuzo
R
Seto
Masao
M
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
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