PVRL2 is translocated to the TRA@ locus in t(14;19)(q11;q13)-positive peripheral T-cell lymphomas

Very few recurrent chromosomal abnormalities have been identified in T-cell non-Hodgkin lymphomas. These involve the TRA@/TRD@ gene at chromosome band 14q11 in up to 15% of cases. We recently reported a novel and recurrent translocation, t(14;19)(q11;q13), in peripheral T-cell lymphoma (PTCL). Fluorescence in situ hybridization analysis performed in three cases suggested an involvement of the TRA@/TRD@ locus at 14q11 and of a region telomeric to BCL3 on 19q13. We now report the molecular cloning of these translocations. Sequence analysis confirmed the involvement of the TRA@/TRD@ and indicated that the breakpoints were located mainly in the TRAJ region. On chromosome 19, our results revealed a new clustering of breakpoints outside the region involved in t(14;19)(q32;q13)-positive B-cell malignancies. Remarkably, all three breaks were located downstream or within the PVRL2 gene, in a small 10.3 kb interval, suggesting a nonrandom location of the breakpoints. For two patients, a high mRNA expression of both PVRL2 and BCL3 was found. In conclusion, we identified PVRL2 as a new recurrent partner gene of the TRA@ locus in PTCL. These results suggest that both BCL3 and PVRL2 may participate in the pathogenesis of these PTCLs, but further studies should be undertaken to investigate the precise role of these genes.