TCR variable gene involvement in chromosome inversion between 14q11 and 14q24 in adult T-cell leukemia

Abstract

Chromosomal translocations in T-cell malignancies frequently involve the T-cell receptor (TCR)a/d locus at chromosome 14q11. Although 14q11 abnormalities are found in about 10% of adult T-cell leukemia (ATL) cases, until now there has been no direct evidence showing involvement of the TCR locus in ATL-a malignancy closely associated with HTLV-1 infection. The breakpoints of T-cell malignancies most commonly occur within the Ja or Jd region of the TCR locus. In ATL, however, despite extensive searching no breakpoint has yet been found in that region. Using fluorescence in situ hybridization with a panel of cosmid and bacterial artificial chromosome probes derived from chromosome 14, including the variable region of the TCRa locus, comprehensive analysis of an ATL patient carrying inv(14)(q11q32) revealed that the TCR locus was indeed involved in this inversion. Molecular cloning of the breakpoint revealed the juxtaposition of TCR Va to the 14q24 region as a result of two consecutive inversions: inv(14)(q11q32) and inv(14)(q11q24). We also found a gene near the breakpoint at the 14q24 region that is downregulated in this ATL patient and is assigned in the database as a pseudogene of ADAM21 (a disintegrin and metalloproteinase domain 21). Our expression analysis, however, showed that this pseudogene was actually expressed and was capable of encoding a protein similar to ADAM21; thus we have named this gene ADAM21-like (ADAM21-L).

Pseudogenes: Newly Discovered Players in Human Cancer

“…Pseudogenes are frequently located in regions of the human genome that undergo chromosomal rearrangements, amplifi cation, deletion, or epigenetic silencing (21,37,(68)(69)(70)(71). Oncogenic pseudogenes may be associated with regions of amplifi cation.…”

The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

“…The translocation (14;14)(q11;q32) is a reciprocal translocation and a variant of inv(14)(q11q32). These rearrangements should not be confused with t(14;14)(q11;q32) and inv(14)(q11q32) seen in T-cell malignancies in ataxiatelangiectasia (AT) patients and non-AT patients ( Bertness et al , 1990 ; Matutes et al , 1991 ; Minegishi et al , 1991 ; Taylor et al , 1996 ; Przybylski et al , 2005 ; Graux et al , 2006 ; Haider et al , 2006 ). The former involves the T-cell receptor (TCR) loci TCRA at 14q11 and TCL1 at 14q32.…”