A molecular study of the t(4;14) in XXXX .

@entity1 @entity10479 @entity2557 @entity535 @entity50598 @entity1582 @entity50601 @entity7639
The t(4;14) translocation is found in approximately 10% of @entity1582 @entity1 and results in the deregulation of at least two genes, @entity50601 and @entity2557 ( @entity2557 ), with the formation of a fusion product between @entity50601 and the @entity7639 ( @entity7639 ) locus and overexpression of @entity2557 . We have analysed a series of 80 @entity1 samples, comprising 67 @entity1582 ( @entity1582 ) cases and 13 @entity10479 ( @entity10479 ) cases, using RT-PCR to detect @entity7639 - @entity50601 fusions. The t(4;14) translocation was detected in 7/67 (10%) @entity1582 cases and all seven expressed @entity2557 which was not seen in t(4;14)-negative @entity1582 cases. In the @entity10479 cases, a similar proportion of t(4;14)-positive cases was found (2/13; 15%), but none of these expressed @entity2557 . All @entity1 with detectable @entity2557 expressed both the @entity2557 IIIb and @entity2557 IIIc isoforms, the result of alternative splicing in the ligand binding domain, and exon-deleted variants of @entity2557 . We also identified a cryptic splice site in @entity50601 which results in a 277 @entity535 deletion downstream of the breakpoint on der(4). @entity2557 mutation analysis revealed no mutations in the presenting @entity1582 or @entity10479 samples. However, we also had access to paired presentation and relapse samples which had been taken from a @entity1 13 months apart. Both samples had the t(4;14) translocation and overexpressed @entity2557 , but only the relapse sample possessed the @entity50598 mutation in the kinase domain of @entity2557 . This suggests that targeted mutation in the translocated @entity2557 gene when under the control of the immunoglobulin promoters can occur and may provide one mechanism for disease progression.
