t(3;9)(q27;p13) GRHPR/BCL6

2012-11-01   Jean-Loup Huret 

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

Clinics and Pathology

Disease

Non Hodgkin lymphoma

Clinics

The t(3;9)(q27;p13) was found in a case of follicular lymphoma transformed to diffuse aggressive lymphoma, from a study with no individual data (Akasaka et al., 2003), in a 71-year-old female patient with a diagnosis of diffuse large B-cell lymphoma (DLBCL) of stomach, which evolved to a nodular lymphocyte-predominant Hodgkins lymphoma 3 years later, and to a nodal DLBCL nine years after the initial diagnosis (Wlodarska et al., 2004), in a 47-year-old male patient with Burkitt lymphoma, who died of progressive disease 2 months after diagnosis (Bacher et al., 2011), and in a female patient with a follicular lymphoma (Cheung et al., 2012).

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). Role in germinal centers of lymphoid follicles. BCL6 prevents ATM and TP53 to induce apoptosis in response to DNA rearrangements such as somatic hypermutation and class switch recombination. Therefore essential for normal B cell development.
Gene name
GRHPR (glyoxylate and hydroxypyruvate reductase)
Location
9p13.2
Note
GRHPR was found involved in the translocation reported in the Akasakas case, and Wlodarska et al., 2004 also point to its possible involvement.
Protein description
GRHPR is an enzyme which catalyzes the reduction of hydroxy-pyruvate to D-glycerate, glyoxylate to glycolate and the oxidation of D-glycerate to hydroxypyruvate. Primary hyperoxaluria type 2 is an autosomal recessive disease caused by mutations in GRHPR (Cramer et al., 1999).

Result of the Chromosomal Anomaly

Description

Breakpoint in BCL6 first intron.

Bibliography

Pubmed IDLast YearTitleAuthors
127386802003BCL6 gene translocation in follicular lymphoma: a harbinger of eventual transformation to diffuse aggressive lymphoma.Akasaka T et al
125550642003Ambivalent role of BCL6 in cell survival and transformation.Albagli-Curiel O et al
209605632011Several lymphoma-specific genetic events in parallel can be found in mature B-cell neoplasms.Bacher U et al
221040782012SNP analysis of minimally evolved t(14;18)(q32;q21)-positive follicular lymphomas reveals a common copy-neutral loss of heterozygosity pattern.Cheung KJ et al
104847761999The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II.Cramer SD et al
153396802004Heterogeneity of BCL6 rearrangements in nodular lymphocyte predominant Hodgkin's lymphoma.Wlodarska I et al

Summary

Fusion gene

GRHPR/BCL6 GRHPR (9p13.2) BCL6 (3q27.3) M|GRHPR/BCL6 GRHPR (9p13.2) BCL6 (3q27.3) M t(3;9)(q27;p13)

Citation

Jean-Loup Huret

t(3;9)(q27;p13) GRHPR/BCL6

Atlas Genet Cytogenet Oncol Haematol. 2012-11-01

Online version: http://atlasgeneticsoncology.org/haematological/2132/t(3;9)(q27;p13)

External Links