Molecular Characterization of Novel Chromosomal Translocations Involved with TCR Locus in T-ALL

Abstract 4409

Chromosomal translocations occur frequently in hematological malignancies, which might involve in cell transformation and initiation of malignancy. In T-cell malignancies, the chromosomal aberrations are more complex due to the TCR gene rearrangements during T-cell differentiation, which provide different breakpoints for the gene recombination. The chromosomal translocations that occur in the cases of T-cell acute lymphocatic leukemia (T-ALL) frequently involve the juxtaposition of enhancer elements and strong promoter from T-cell receptor (TCR) genes on chromosome 14 (TCRA and TCRD) and chromosome 7 (TCRB and TCRG) with transcription factors genes. Using a novel rapid approach of fine-tiling array comparative genomic hybridization (fine-tiling aCGH) with the array coving the TCR&brkbar;Á&brkbar;Ä, TCR&brkbar;Ã and TCR&brkbar;Â loci, chromosomal alterations were analyzed and the breakpoints and their position in the chromosomes in genomic DNA were identified from patients with T-ALL.

Combining with ligation-mediated PCR (LM-PCR) and sequencing techniques, we clarified at the molecular level novel chromosomal translocation t(X;14)(q11.2;q11), inv(14)(q11;q11), t(1;14)(p32;q11), inv(14)(q11;q32) and t(7;14)(q34;q32) in 4 cases with T-ALL. which caused a V&brkbar;Á37 segment fused to ZFRP1 gene locus, J&brkbar;Á61 segment fused to RPSAP4 gene locus, V&brkbar;Â20 segment rearranged to Ig&brkbar;Ê gene segment and so on. The biological function of the novel fusion genes is needed further research.