A novel gene, FGA7, is fused to RUNXI/AMLI in a t(4;21)(q28;q22) in a patient with T-cell acute lymphoblastic leukemia

作者：Mikhail FM; Coignet L; Hatem N; Mourad ZI; Farawela HM; El Kaffash DM; Farahat N; Nucifora G^*

来源：Genes, Chromosomes and Cancer, 2004, 39(2): 110-118.

DOI：10.1002/gcc.10302

AMLI is among the most frequent targets of chromosomal rearrangements inhuman leukemias. We report here the molecular analysis of a t(4;21)(q28;q22) that has disrupted AMLI in a patient with de novo T-cell acute lymphoblastic leukemia. By using 3'-RACE analysis, we show that this rearrangement results in the fusion of a novel gene immediately downstream of exon 5 or exon 6 of AMLI, indicating that the AMLI breakpoint lies in intron 6 and that alternative fusion splice variants are generated. The sequence of the novel gene, located at 4q28, does not have any significant homology with any of the known genes in the with mouse and rat sequences suggests that this sequence most probably represents a part of a novel gene, which we named FGA7 (Fused Gene 7 to AMLI. Following the AMLI open reading frame, the FGA7 sequence encodes an unknown protein of 27 amino acids. We isolated three bacterial artificial chromosome (BAC) clones that contain the FGA7 sequence and confirmed the breakpoint of the gene on the patient's metaphase spreads by fluorescence in situ hybridization using these BACs as probes. RT-PCR and Northern blot analyses revealed that FGA7 is expressed in ovarian and skeletal muscle tissues. The predicted AMLIFGA7 chimeric proteins contained a limited number of residues fused to AMLI in a situation similar to that reported for the AMLI-EAPfusion that is a product of t(3;21). It is possible that the expression of a constitutively shortened AMLI could compete with full-length AMLI and act as a dominant negative inhibitor of the promoters that the core binding factor activates.

• 出版日期2004-2