A variant chromosome translocation at 11q13 identifying PRAD1/cyclin D1 as the BCL-1 gene

Abstract

The 11q13 breakpoint region of t(11;14) (q13;q32), translocated to the Ig heavy chain locus at 14q32, has been designated as BCL-1 for B-cell leukemia/lymphoma-1, but the nature of the transcriptional unit has long remained unclear. Recently, the PRAD1 gene encoding cyclin D1, isolated from the 11q13 region, was proposed as a candidate BCL-1 gene on the basis of chromosome walking and concordant overexpression of PRAD1 mRNA in cell lines with t(11;14)(q13;q32). We report here molecular analysis of a variant translocation at the BCL-1 locus, t(11;22)(q13;q11), showing juxtaposition of the Ig light chain gene, Ig lambda, to the PRAD1 gene at its 3′ end, resulting in overexpression of PRAD1 mRNA. Because only the PRAD1 gene is present between the Ig heavy chain and light chain gene breakpoints, an identity between BCL-1 and the PRAD1/cyclin D1 gene is strongly indicated.

Molecular cloning of IGλ rearrangements using long‐distance inverse PCR (LDI‐PCR)

“…(B) Two breakpoints of der(11)t(11;22)(q13;q11) are in the 3′ UTR of CCND 1 . Arrow indicates a breakpoint cloned in this study, whereas dotted arrow indicates a previous report . Solid boxes and dotted boxes indicate coding and non‐coding regions, respectively.…”

Heterogeneous pattern of chromosomal breakpoints involving the MYC locus in multiple myeloma

“…In Burkitt lymphoma, breakpoints telomeric to MYC specifically involve the IGL@ loci, mainly IGL@ at 22q11. This finding has also been reported for breakpoints involving regions telomeric to BCL2 in follicular lymphoma and CCND1 in mantle cell lymphoma (Taub et al, 1984;Adachi et al, 1989;Komatsu et al, 1994). Although there is no clear explanation for this finding in MM, it is worth noting that telomeric MYC breakpoints seem to be associated with complex, non-reciprocal chromosomal rearrangements.…”

3′ BCR recombines with IGL locus in BCRABL–positive Philadelphia‐negative chronic myeloid leukemia

“…Consistent with a mechanism of origin common to normal somatic expression of the Ig loci, genes found aberrantly linked with IGL are in large part variant rearrangements involving the same genes found linked to IGH or IGK and occur in the same subgroups of B-cell malignancies. Examples include fusion of IGL with MYC on chromosome band 8q24, associated with a t(8;22)(q24;q11) (Hollis et al, 1984;Showe et al, 1987); BCL1 at 11q13 associated with a t(11;22)(q13;q22) (Komatsu et al, 1994); BCL2 at 18q21 associated with a t(18;22)(q21;q11) (Adachi et al, 1989;Tashiro et al, 1992); and BCL6 at 3q27 associated with a t(3;22)(q27;q11) (Miki et al, 1994).…”

“…These IGL rearrangements are therefore thought to arise because of misjoining and misrepair by a V(D)J recombinase, a mechanism similar to that proposed to underlie formation of IGH and IGK fusion genes in the lymphoid disorders (Showe et al, 1987;Tashiro et al, 1992;Miki et al, 1994). Some cases, however, show no recombinase-specific sequence features around the recombination sites (Adachi et al, 1989;Seite et al, 1993b;Komatsu et al, 1994), and other factors are proposed to mediate breakage and misjoining (Adachi and Tsujimoto, 1990;Seite et al, 1993a).…”