Molecular Characterization of a Novel Chromosomal Translocation t(12;14)(q23;q11.2) in T-Lymphoblastic Lymphoma Between the T Cell Receptor Delta Deleting Elements (TRDREC and TRAJ61) and the Hypothetical Gene C12orf42.

Abstract 4239

Chromosomal aberrations have diagnostic, prognostic and therapeutic consequences in haematological malignancies. By combining fine-tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR) we established a fast and robust approach to precisely characterize chromosomal breakpoints. Using this approach we characterized at the molecular level novel chromosomal translocation t(12;14)(q23;q11.2) in T-lymphoblastic lymphoma occurring during the deletional rearrangement of the T cell receptor delta gene (TRD). Normally, this transient rearrangement is a pivotal step in T cell differentiation towards the alpha/beta versus the gamma/delta lineage and generates the T cell receptor excision circles (TREC), which are quantitated to determine the proliferative history of T cells. We found that the rearrangement disrupted the hypothetical gene C12orf42 and brought the Achaete-scute complex homolog 1 (ASCL1) gene into proximity to the TRA enhancer, which is encodes a member of the basic helix-loop-helix (BHLH) family of transcription factors and is overexpressed in medullary thyroid cancer and small cell lung cancer.