t(3;12)(q27;p13) GAPDH/BCL6

2010-01-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Non Hodgkin lymphomas (NHL)

Epidemiology

One case to date, a 78-year-old female patient with a multifocal lymphoma, CD20+ diffuse large B-cell lymphoma (DLBCL) type, presenting as a primary central nervous system lymphoma (PCNSL) (Montesinos-Rongen et al., 2003). PCNSL are extra nodal NHL localized to -and remaining in- the central nervous system.

Genes Involved and Proteins

Gene name
BCL6 (B-Cell Lymphoma 6)
Location
3q27.3
Protein description
706 amino acids; composed of a NH2-term BTB/POZ domain (amino acids 1-130 (32-99 according to Swiss-Prot) which mediates homodimerization and protein-protein interactions with other corepressors (including HDAC1 and NCOR2/SMRT ) to constitute a large repressing complex, another transcription repression domain (191-386), PEST sequences (300-417) with a KKYK motif (375-379), and six zinc finger at the C-term (518-541, 546-568, 574-596, 602-624, 630-652, 658-681), responsible for sequence specific DNA binding. Transcription repressor; recognizes the consensus sequence: TTCCT(A/C)GAA (Albagli-Curiel, 2003).
Gene name
GAPDH (glyceraldehyde-3-phosphate dehydrogenase)
Location
12p13.31
Protein description
335 amino acids; possess a nucleotide binding site for NAD+, and sites for glyceraldehyde 3-phosphate binding; catalyzes the phosphorylation and oxidation of glyceraldehyde-3-phosphate to 1,3-biphosphoglycerate (interconversion), using NAD+ as electron acceptor. Role in endocytosis and in nuclear membrane assembly. Associates with microtubules and RAB2, which stimulates the recruitment of dynein, to regulates microtubule motility and cargo transport. Also binds mRNA and t-RNA; may participate in tRNA export and mRNA stability. Role in the cell cycle, in DNA repair, and in apoptosis associated with oxidative stress (reviews in Sirover, 1999; Hara and Snyder, 2006; Hara et al., 2006; Colell et al., 2009).

Result of the Chromosomal Anomaly

Description

Breakpoint in the intron 2 of GAPDH; leads to the juxtaposition of the GAPDH promotor region with the 2 first exons and the entire BCL6, inducing deregulated expression of BCL6.

Bibliography

Pubmed IDLast YearTitleAuthors
125550642003Ambivalent role of BCL6 in cell survival and transformation.Albagli-Curiel O et al
197794982009Novel roles for GAPDH in cell death and carcinogenesis.Colell A et al
165743842006GAPDH as a sensor of NO stress.Hara MR et al
166338962006Nitric oxide-GAPDH-Siah: a novel cell death cascade.Hara MR et al
146557582003Molecular characterization of BCL6 breakpoints in primary diffuse large B-cell lymphomas of the central nervous system identifies GAPD as novel translocation partner.Montesinos-Rongen M et al
104071391999New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase.Sirover MA et al

Summary

Fusion gene

GAPDH/BCL6 GAPDH (12p13.31) BCL6 (3q27.3) M|GAPDH/BCL6 GAPDH (12p13.31) BCL6 (3q27.3) M t(3;12)(q27;p13)|GAPDH/BCL6 GAPDH (12p13.31) BCL6 (3q27.3) TIC

Citation

Jean-Loup Huret

t(3;12)(q27;p13) GAPDH/BCL6

Atlas Genet Cytogenet Oncol Haematol. 2010-01-01

Online version: http://atlasgeneticsoncology.org/haematological/1337/t(3;12)(q27;p13)

External Links