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

Abstract

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.

Peripheral T-cell lymphoma cell line T8ML-1 highlights conspicuous targeting of PVRL2 by t(14;19)(q11.2;q13.3)

“…[4][5][6][7] In the absence of corresponding expression data, the proximity of BCL3 and PVRL2 (located ~86 kbp apart) has obscured which (if either) is the true target.…”

Tricky and Terrible T-Cell Tumors: These are Thrilling Times for Testing: Molecular Pathology of Peripheral T-Cell Lymphomas

“…[33][34][35][36] PVRL2 (poliovirus receptor-related 2) has been cloned as the partner gene of the TRA@ in the t(14;19)(q11;q13) translocation and appears to be associated with overexpression of both PVRL2 and BCL3 mRNAs. 37,38 Recently, involvement of the multiple myeloma oncogene-(MUM1)/ IFN-regulatory factor-4 (IRF4) oncogene locus in chromosomal translocations involving the TRA@ gene, t(6;14)(p25;q11.2), was identified in 2 cases of PTCL, NOS with a cytotoxic phenotype and a peculiar clinical presentation characterized by involvement of the bone marrow and skin without significant lymphadenopathy or hepatosplenomegaly. The marked similarity between the 2 cases with IRF4/TRA@ translocation suggests that they may represent a distinct clinicopathologic entity.…”

A rare case of Lennert’s type peripheral T‐cell lymphoma with t(14;19)(q11.2;q13.3)

“…Intact, co‐localized green and red signals without any evidence of rearrangement were observed in FISH analysis with both pairs of BAC clones, suggesting the involvement of genes distal to BCL3 and PVRL2 (Figure 2d). Reverse transcription‐polymerase chain reaction (RT‐PCR) for PVRL2 rearrangement, a near distal candidate oncogene, performed as described (Almire et al. , 2007), yielded no PCR product.…”

“…The cytogenetic and molecular properties of Lennert’s type PTCL have not been well characterized. Rearrangements of TCR genes into genes located at 19q13.3 have rarely been reported in T‐cell lymphoma (Almire et al. , 2007).…”