The mechanism of chromosome 14 inversion in a human T cell lymphoma

The chromosome 14 inversion produces cytogenetic breakpoints at either end of the long arm of this chromosome. Previous studies have shown that a hybrid gene (designated IgT) consisting of an immunoglobulin VH gene segment and T cell receptor J alpha C alpha segments encompasses the telomeric breakpoint in SUP-T1, a cell line derived from a human T cell lymphoma. Here, we report that the centromeric breakpoint in SUP-T1 constitutes the reciprocal of a VH-J alpha join but involves gene segments different from those at the telomeric breakpoint. Therefore, chromosome inversion and IgT formation were mediated by two sequential VH-J alpha joining events. Moreover, sequences adjacent to the centromeric breakpoint detect a T-cell-specific RNA, encoded within the immunoglobulin VH locus, whose transcriptional activity may have facilitated the illegitimate VH-J alpha rearrangements.