B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

“…In several cases of human B-and T-cell lymphomas, genetic rearrangements at chromosome 10q24 are associated with structural alterations of the NFKB2 gene, resulting in production of truncated NFkB-2 proteins with heterogeneous C-terminal ends (Fracchiolla et al, 1993 ;Migliazza et al, 1994;Neri et al, 1991Neri et al, , 1996Thakur et al, 1994). Such alterations have been particularly associated with cutaneous T cell lymphomas; anywhere from 3 ± 5% to 15 ± 20% of CTCL samples have been reported to have NFKB2 gene alterations (Migliazza et al, 1994;Thakur et al, 1994).…”

“…Rearrangements of the NFKB2 gene have been associated with both B-cell and T-cell malignancies, and NF-kB-2 was identi®ed to be rearranged in up to 15 ± 20% of cutaneous T-cell lymphomas (CTCL) [(Fracchiolla et al, 1993;Migliazza et al, 1994;Neri et al, 1991;Thakur et al, 1994) and reviewed in (Neri et al, 1996)]. The molecular structures of several tumorassociated NFKB2 alleles have been described (Fracchiolla et al, 1993;Migliazza et al, 1994;Neri et al, 1991;Thakur et al, 1994;Zhang et al, 1994). These proteins all exhibit truncations of the C-terminal ankyrin repeats present in p100 NF-kB-2.…”

“…These proteins all exhibit truncations of the C-terminal ankyrin repeats present in p100 NF-kB-2. The Lyt-10/Ca variant of NFKB2 was identi®ed from a case of B-cell non-Hodgkin's lymphoma (RC685) (Neri et al, 1991) and is a chimeric protein in which the ®rst ankyrin repeat of NF-kB-2 is fused in frame to a 174 amino acid alternative reading frame derived from the immunoglobulin Ca gene. The HUT78 p80HT (also referred to as p85, as well as p84, an alternatively spliced form of the protein), was derived from a CTCL cell line, and is a truncated form of NF-kB-2 that maintains ®ve ankyrin repeats fused to repetitive DNA sequences (Thakur et al, 1994;Zhang et al, 1994), resulting in the fusion of the ®rst 666 amino acids of p100 NF-kB-2 to three extra amino acids (serinealanine-serine) derived from the fusion sequence.…”

Mutations in the NF-κB signaling pathway: implications for human disease

“…These rearrangements in NFKB2 can be due to chromosomal translocations or chromosomal deletions. In some cases, these changes probably come about as a consequence of aberrant immune cell gene rearrangement; for example, in one B-cell lymphoma, a chromosomal translocation results in exons encoding residues from the constant region of the immunoglobulin heavy chain being placed just 3 0 to exons encoding the RHD of p100, suggesting that incorrect class switching generated the hybrid locus (Neri et al, 1991). More recently, a point mutation in exon 21 of NFKB2 that creates a stop codon at 775, has been detected in several human B-and T-cell lines, including the well-known Jurkat and Daudi cell lines (Derudder et al, 2003).…”

Identification of a tumor-associated mutant form of the NF-κB RelA gene with reduced DNA-binding and transactivating activities

“…c-Rel gene has been found to be rearranged in some cases of lymphoid neoplasia (Lu et al, 1991), whereas ampli®cation is frequently associated with extranodal di use large cell lymphomas (DLCL) (Houldsworth et al, 1996). Rearrangements of the NFKB2/lyt-10 gene can be found at low frequency in B-cell lymphoma, B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM), and more commonly in cutaneous lymphomas (CL), as a consequence of chromosomal translocations or, more frequently, internal deletions (Neri et al, 1991;Fracchiolla et al, 1993;Migliazza et al, 1994). The bcl-3 gene has been found to be involved in a t(14;19) chromosomal translocation in some cases of clinically aggressive B-CLL (Ohno et al, 1990).…”