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t(3;14)(q27;q32) HSP90AA1/BCL6

Written2013-01Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 1356
Note Most of the t(3;14)(q27;q32) where molecular genetics studies were performed showed the involvement of IGH@ and BCL6. It is unknown if the prognoses are different.

Clinics and Pathology

Disease Non Hodgkin lymphoma
Clinics Four cases available to date: a case of primary gastric lymphoma (Xu et al., 2000); a gastric diffuse large B-cell lymphoma with residual MALT lymphoma (DLCLML) case (Chen et al., 2006), a case of primary central nervous system lymphoma (PCNSL, a diffuse large B cell lymphoma confined to the brain) (Montesinos-Rongen et al., 2003), and another lymphoma case (Akasaka et al., 2000).

Genes involved and Proteins

Gene Name BCL6
Location 3q27.3
Protein 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 HSP90AA1
Location 14q32.31
Protein HSP90AA1 is also known as HSP90. Molecular chaperone. Possesses an ATP binding site with intrinsic ATPase activity that regulates its conformation. Promotes the maturation, structural maintenance and regulation of specific target proteins called 'client' proteins. Maintains protein homeostasis. HSP90AA1/HSP90 interacts with regions of client proteins where protein folding clefts merge. Folding clefts are a general topological feature of proteins in native conformation, and many of these hydrophobic clefts, must open to permit access of ligands. HSP90AA1/HSP90 stabilizes the open cleft, impeding further unfolding and Hsp70-dependent ubiquitination (Pratt et al., 2010). HSP90AA1/HSP90 and its associated co-chaperones facilitate a precise and efficient working environment beneficial for telomere function (DeZwaan and Freeman, 2010). HSP90AA1/HSP90 is exploited by cancer cells to support the activated and/or metastable forms of oncoproteins, and to buffer cellular stresses induced by the malignancy. Hsp90 is often overexpressed in cancer cells (Neckers and Workman, 2012).

Result of the chromosomal anomaly

Hybrid gene
Description The break occurs in HSP90AA1 intron 1, resulting in the exchange of the first non-coding exons of HSP90AA1 and BCL6.
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

Molecular anatomy of BCL6 translocations revealed by long-distance polymerase chain reaction-based assays.
Akasaka H, Akasaka T, Kurata M, Ueda C, Shimizu A, Uchiyama T, Ohno H.
Cancer Res. 2000 May 1;60(9):2335-41.
PMID 10811103
 
Ambivalent role of BCL6 in cell survival and transformation.
Albagli-Curiel O.
Oncogene. 2003 Jan 30;22(4):507-16.
PMID 12555064
 
High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma.
Chen YW, Hu XT, Liang AC, Au WY, So CC, Wong ML, Shen L, Tao Q, Chu KM, Kwong YL, Liang RH, Srivastava G.
Blood. 2006 Oct 1;108(7):2373-83. Epub 2006 Jun 13.
PMID 16772602
 
HSP90 manages the ends.
DeZwaan DC, Freeman BC.
Trends Biochem Sci. 2010 Jul;35(7):384-91. doi: 10.1016/j.tibs.2010.02.005. Epub 2010 Mar 16. (REVIEW)
PMID 20236825
 
Molecular 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, Akasaka T, Zhlke-Jenisch R, Schaller C, Van Roost D, Wiestler OD, Siebert R, Deckert M.
Brain Pathol. 2003 Oct;13(4):534-8.
PMID 14655758
 
Hsp90 molecular chaperone inhibitors: are we there yet?
Neckers L, Workman P.
Clin Cancer Res. 2012 Jan 1;18(1):64-76. doi: 10.1158/1078-0432.CCR-11-1000. (REVIEW)
PMID 22215907
 
Proposal for a role of the Hsp90/Hsp70-based chaperone machinery in making triage decisions when proteins undergo oxidative and toxic damage.
Pratt WB, Morishima Y, Peng HM, Osawa Y.
Exp Biol Med (Maywood). 2010 Mar;235(3):278-89. doi: 10.1258/ebm.2009.009250. (REVIEW)
PMID 20404045
 
Identification and characterization of BCL6 translocation partner genes in primary gastric high-grade B-cell lymphoma: heat shock protein 89 alpha is a novel fusion partner gene of BCL6.
Xu WS, Liang RH, Srivastava G.
Genes Chromosomes Cancer. 2000 Jan;27(1):69-75.
PMID 10564588
 

Citation

This paper should be referenced as such :
Huret JL
t(3;14)(q27;q32) HSP90AA1/BCL6;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0314q27q32ID1356.html


Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes BCL6

Translocations implicated (Data extracted from papers in the Atlas)

 t(3;14)(q27;q32) HSP90AA1/BCL6

External links

arrayMap (UZH-SIB Zurich)
Mitelman databaset(3;14)(q27;q32) [Case List]    t(3;14)(q27;q32) [Association List] Mitelman database (CGAP - NCBI)
arrayMap[select an item]
 
 
Disease databaset(3;14)(q27;q32) HSP90AA1/BCL6
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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