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t(8;9)(q24;p13) ?/MYC

Written2013-10Jean-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
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 2141

Clinics and Pathology

Disease B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)
Phenotype / cell stem origin There were 5 cases of ALL (L3-ALLs and CD10+ ALLs in 2 cases each), 11 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of unclassifiable B-cell lymphoma, one case of follicular lymphoma, and one case of diffuse mixed small and large cell lymphoma (Levine et al., 1989; Nacheva et al., 1993; Dunphy et al., 2003; D'Achille et al., 2006; Bertrand et al., 2007; Le Gouill et al., 2007; Christie et al., 2008; Johnson et al., 2009; Subramaniyam et al., 2011).
Epidemiology Twenty five cases are available. There were 12 male and 13 female patients, median age was 63 years (range 42-90 years). In a review of NHLs with a t(14;18)(q32;q21), the incidence of MYC translocations was 5%, and the incidence of t(8;9)(q24;p13) was 1% (Johansson et al., 1995).
 
Meta-analysis of survival in patients with t(8;9)(q24;p13).
Prognosis Median survival was 4 months (see figure). However, patients with an ALL died at 1, 1, 1.5, and 1.5 months. Median survival of patients with NHL was 6 months, and 3 out of 19 NHL patients were still alive 5 years after diagnosis (16%).

Cytogenetics

Cytogenetics Morphological A t(14;18)(q32;q21) was present in 24 of 25 cases, including 5 of the 5 cases of ALL, a complex karyotype was found in 24 of 25 cases. Trisomy 7 and 12 were found in seven cases each, trisomy 11 and 21, and del(6q) in four cases each, trisomy 20 in three cases, trisomy 8, 13, and 18, t(1;22)(q21;q11), del(3p), and del(3q) in two cases each.

Genes involved and Proteins

Note Breakpoints occurred close to MYC on chromosome 8 and close to: ZBTB5, ZCCHC7, and PAX5 on chromosome 9 (Bertrand et al., 2007; Le Gouill et al., 2007; Johnson et al., 2009).
- ZBTB5 is a POZ domain Krüppel-like zinc finger transcription repressor. ZBTB5 interacted with co-repressor-histone deacetylase complexes such as BCOR, NCOR1, and NCOR2 (SMRT), resulting in deacetylation of histones Ac-H3 and Ac-H4, and transcriptional repression of CDKN1A (p21) (Koh et al., 2009).
- ZCCHC7 is the equivalent of the yeast AIR1. In yeast, a number of unwanted RNA transcripts are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. TRAMP facilitates pre-mRNA splicing (Kong et al., 2013).
- PAX5 is a lineage-specific transcription factor; recognizes the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is any nucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes and represses genes involved in other lineage commitments. Activates the surface cell receptor CD19 and represses FLT3. PAX5 physically interacts with the RAG1/RAG2 complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells are restored in their function in mature B cells and plasma cells, and PAX5 repressed (Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007).
Gene NameMYC v-myc myelocytomatosis viral oncogene homolog (avian)
Location 8q24.21
Protein DNA binding protein. Binds DNA as a heterodimer with MAX. Involved in various cellular processes including cell growth, proliferation, cell adhesion, apoptosis, angiogenesis, and stem cell behaviour modulation.

Result of the chromosomal anomaly

Fusion Protein
Expression Localisation There was abundant MYC expression in all the cases studied.
  

Bibliography

Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas.
Bertrand P, Bastard C, Maingonnat C, Jardin F, Maisonneuve C, Courel MN, Ruminy P, Picquenot JM, Tilly H.
Leukemia. 2007 Mar;21(3):515-23. Epub 2007 Jan 18.
PMID 17230227
 
C-MYC translocation in t(14;18) positive follicular lymphoma at presentation: An adverse prognostic indicator?
Christie L, Kernohan N, Levison D, Sales M, Cunningham J, Gillespie K, Batstone P, Meiklejohn D, Goodlad J.
Leuk Lymphoma. 2008 Mar;49(3):470-6. doi: 10.1080/10428190701836845.
PMID 18297523
 
Pax5: the guardian of B cell identity and function.
Cobaleda C, Schebesta A, Delogu A, Busslinger M.
Nat Immunol. 2007 May;8(5):463-70. (REVIEW)
PMID 17440452
 
Translocation (14;18)(q32;q21) in acute lymphoblastic leukemia: a study of 12 cases and review of the literature.
D'Achille P, Seymour JF, Campbell LJ.
Cancer Genet Cytogenet. 2006 Nov;171(1):52-6. (REVIEW)
PMID 17074591
 
Mature B-cell acute lymphoblastic leukemia with associated translocations (14;18)(q32;q21) and (8;9)(q24;p13). A Burkitt variant?
Dunphy CH, van Deventer HW, Carder KJ, Rao KW, Dent GA.
Arch Pathol Lab Med. 2003 May;127(5):610-3. (REVIEW)
PMID 12708908
 
Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.
Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M.
Genes Dev. 2004 Feb 15;18(4):411-22.
PMID 15004008
 
Cytogenetic evolution patterns in non-Hodgkin's lymphoma.
Johansson B, Mertens F, Mitelman F.
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PMID 7579360
 
B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.
Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K.
Nat Immunol. 2004 Aug;5(8):853-61. Epub 2004 Jul 18.
PMID 15258579
 
Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival.
Johnson NA, Savage KJ, Ludkovski O, Ben-Neriah S, Woods R, Steidl C, Dyer MJ, Siebert R, Kuruvilla J, Klasa R, Connors JM, Gascoyne RD, Horsman DE.
Blood. 2009 Sep 10;114(11):2273-9. doi: 10.1182/blood-2009-03-212191. Epub 2009 Jul 13.
PMID 19597184
 
A novel POK family transcription factor, ZBTB5, represses transcription of p21CIP1 gene.
Koh DI, Choi WI, Jeon BN, Lee CE, Yun CO, Hur MW.
J Biol Chem. 2009 Jul 24;284(30):19856-66. doi: 10.1074/jbc.M109.025817. Epub 2009 Jun 2.
PMID 19491398
 
Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing.
Kong KY, Tang HM, Pan K, Huang Z, Lee TH, Hinnebusch AG, Jin DY, Wong CM.
Nucleic Acids Res. 2013 Oct 3. [Epub ahead of print]
PMID 24097436
 
The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement.
Le Gouill S, Talmant P, Touzeau C, Moreau A, Garand R, Juge-Morineau N, Gaillard F, Gastinne T, Milpied N, Moreau P, Harousseau JL, Avet-Loiseau H.
Haematologica. 2007 Oct;92(10):1335-42.
PMID 18024371
 
Four new recurring translocations in non-Hodgkin lymphoma.
Levine EG, Arthur DC, Machnicki J, Frizzera G, Hurd D, Peterson B, Gajl-Peczalska KJ, Bloomfield CD.
Blood. 1989 Oct;74(5):1796-800.
PMID 2506953
 
C-MYC translocations in de novo B-cell lineage acute leukemias with t(14;18)(cell lines Karpas 231 and 353).
Nacheva E, Dyer MJ, Fischer P, Stranks G, Heward JM, Marcus RE, Grace C, Karpas A.
Blood. 1993 Jul 1;82(1):231-40.
PMID 8324225
 
De novo B lymphoblastic leukemia/lymphoma in an adult with t(14;18)(q32;q21) and c-MYC gene rearrangement involving 10p13.
Subramaniyam S, Fraser CR, Rao PH, Feldman E, Ely S, Mathew S.
Leuk Lymphoma. 2011 Nov;52(11):2195-9. doi: 10.3109/10428194.2011.589548. Epub 2011 Jun 30.
PMID 21718139
 
Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.
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PMID 16680144
 

Citation

This paper should be referenced as such :
Huret, JL
t(8;9)(q24;p13) /MYC
Atlas Genet Cytogenet Oncol Haematol. 2014;18(4):282-284.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0809q24p13ID2141.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(8;9)(q24;p13) ?/MYC

External links

Mitelman databaset(8;9)(q24;p13) [Case List]    t(8;9)(q24;p13) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(8;9)(q24;p13) ?/MYC
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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