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t(8;14)(q24;q32) IGH/MYC

t(2;8)(p12;q24) IGK/MYC

t(8;22)(q24;q11) IGL/MYC

Written1999-02Chrystèle Bilhou-Nabera
Cytogénétique,Laboratoire d'Hématologie-Pr RAPHAEL, Pav BROCA - 4me étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France
Updated2016-05Eva van den Berg, Marian Stevens-Kroef
Department of Genetics, University Medical Centre Groningen, Groningen; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands

(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 1050
Note The 3 translocations are variants of each other, and they share the same clinical significance.
 
  Top row: t(2;8)(p12;q24) G- banding - Courtesy Diane H.Norback, Eric B. Johnson, Sara Morrison-Delap; R- banding - (middle right) Courtesy Jean-Luc Lai; (right) Courtesy Hossein Mossafa; below: Courtesy Roland Berger. Middle rows: t(8;14)(q24;q32) G- banding - (left, middle left, center) Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap; R- banding - middle right Courtesy Jean-Luc Lai; right: Jean Loup Huret; below: Courtesy Roland Berger. Lower row: t(8;22)(q24;q11) G- banding (left and center) - Courtesy Diane H. Norback, Eric B.Johnson, Sara Morrison-Delap UW Cytogenetic Services; R- banding - (right) Courtesy Jacques Boyer.

Clinics and Pathology

Disease Described both in B-cell acute lymphoblastic leukemia (ALL) and in non-Hodgkin lymphomas (NHL), especially in Burkitt lymphoma , and 'double-hit' diffuse large B-cell lymphomas (DLBCL).
Phenotype / cell stem origin The postulated normal counterpart is the germinal centre or post-germinal centre B-cell.
Epidemiology Most Burkitt lymphoma cases show the t(8;14)(q24;q32) [MYC-IGH] and less commonly the t(8;22)(q24;q11) or t(2;8)(p12;q24). The translocation is present in both the endemic African Burkitt lymphoma and in the non endemic tumor type (Europe, America, and Japan). In case the Burkitt lymphoma infiltrated the bone marrow (leukemic phase) the MYC-translocation can be demonstrated in the bone marrow or blood as well. If no immunophenotyping results are available, it is good practice to exclude a BCL2 rearrangement because a t(8;14) can be observed in other B cell neoplasms (such as double hit DLBCL see below).
Some DLBCL ('double-hit') cases contain the t(8;14) translocation. In some clinical studies patients with DLBCL and MYC rearrangement will receive more aggressive treatment.
The disease defines the prognosis. Given the correct treatment regime Burkitt lymphoma patients do well, while the outcome in double-hit DLBCL patient is totally different.
Cytology ALL : L3 morphology according to the FAB classification, very occasionally L1 or L2 cytology reported.
 
Bone marrow sample: the medium-sized cells show a diffuse monotonous pattern of infiltration. The nuclei are round, cytoplasm deeply basophilic and usually contain vacuoles. The morphological feature in this bone marrow smear (Giemsa), quite similar to tumor cells as seen in tissue imprints, is highly characteristic of Burkitt lymphoma - Text and iconography Courtesy Georges Flandrin 2005.

Cytogenetics

 
  944B18 The figure illustrates the translocation of the MYC gene (probe 944B18, red) to 14q32.3 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Cytogenetics Morphological t(8;14) is described in 75-85% of the cases, t(2;8) in 5%, and t(8 ;22) in the remaining 10%; high-quality metaphases are required to detect t(8;14) and t(8;22).
Additional anomalies Reported in 70% cases in Burkitt lymphoma and DLBCL, especially: t(14;18)(q32;q21) in double-hit DLBCL lymphoma's, structural rearrangements of the long arm of chromosome 1 (30% cases) resulting in a partial trisomy 1q, rearrangements of 13q34 (15% cases).
Variants t(2;8)(p12;q24) and t(8;22)(q24;q11) are variants of the t(8;14)(q24;q32); three-way rearrangements and translocations of submicroscopic chromosome fragments have also been described.

Genes involved and Proteins

Note On the molecular point of view, in all these three translocations, the gene MYC is juxtaposed either with the immunoglobulin heavy chain locus IGH (14q32), the kappa light-chain locus IGK (2p12), or the lambda light-chain locus IGL (22q11); all these translocations share a breakpoint in 8q24 (MYC locus). The MYC breakpoints are diverse and distributed over a 2Mb region. Therefore it has to be noted that not all MYC-rearrangements can be detected by FISH.
Gene Name MYC
Location 8q24
 
Dna / Rna The human MYC gene belongs to a small gene family with closely related members (MYC, MYCN, MYCL); MYC has three exons; two promoters P1 and P2 control the MYC transcription.
Protein Myc protein is a transcription factor of the helix-loop-helix/leucine zipper family that activates transcription as obligate heterodimer with a partner protein, MAX.
Gene Name IGH
Location located in 14q32
Note Or other Immunoglobulin genes IGK, IGL located in 2p12 and 22q11 respectively.

Result of the chromosomal anomaly

Hybrid gene
Note No hybrid transcript. The translocation leads to the MYC gene under direct regulation of the enhancer of the IGH (or IGK/IGL genes), thereby causing high level transcription of the MYC gene .
Description MYC is translocated to der(14) in the t(8;14), whereas it remains on der(8) in the variant translocations; t(8;14) leads to a head-to-head fusion of MYC with the heavy chain immunogloulin locus : 8q24 is close to the 5' extremity of MYC exon 2, leading the all translated gene region to 14q32; the 8q24 breakpoint region is variable, scattered over a 190 Kb region, 5' far from MYC or within MYC; the 14q32 breakpoint region is mainly located in the constant region, very close within the switch or joining regions; MYC juxtaposed to the immunoglobin constant regions and enhancer is overexpressed, shutting down the normal remaining MYC; in both t(2;8) and t(8;22), the breakpoint is in 3' of or distal to the MYC gene which always remains on der(8); the rearrangement with respectively IGK or IGL and MYC is head-to-tail.
  
Fusion Protein
Note The protein MYC resulting from the translation of the second and third exons, through DNA- binding properties, plays a role in regulating cell growth and differentiation.
Oncogenesis Constitutive expression of MYC induces proliferation even in the absence of growth factors
  

To be noted

Case Report Translocation t(8;14)(q24;q32) as a clue for the diagnosis of B cell prolymphocytic leukemia

Bibliography

World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (12) : 3835-3849.
PMID 10577857
 
Molecular biology of Burkitt's lymphoma.
Hecht JL, Aster JC
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000 ; 18 (21) : 3707-3721.
PMID 11054444
 
Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature.
Kornblau SM, Goodacre A, Cabanillas F
Hematological oncology. 1991 ; 9 (2) : 63-78.
PMID 1869243
 
Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy.
Longo DL, Duffey PL, Jaffe ES, Raffeld M, Hubbard SM, Fisher RI, Wittes RE, DeVita VT Jr, Young RC
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994 ; 12 (10) : 2153-2159.
PMID 7523607
 
Clinicopathogenetic significance of chromosomal abnormalities in patients with blastic peripheral B-cell lymphoma. Kiel-Wien-Lymphoma Study Group.
Schlegelberger B, Zwingers T, Harder L, Nowotny H, Siebert R, Vesely M, Bartels H, Sonnen R, Hopfinger G, Nader A, Ott G, Müller-Hermelink K, Feller A, Heinz R
Blood. 1999 ; 94 (9) : 3114-3120.
PMID 10556197
 
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW.
4th Edition; Lyon, France: IARC Press; 2008.
 

Citation

This paper should be referenced as such :
van den Berg E, Stevens-Kroef M
t(8;14)(q24;q32) IGH/MYC; t(2;8)(p12;q24) IGK/MYC; t(8;22)(q24;q11) IGL/MYC;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0814ID1050.html
History of this paper:
Bilhou-Nabera, C. t(8;14)(q24;q32) - t(2;8)(p12;q24) - t(8;22)(q24;q11). Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):82-84.
http://documents.irevues.inist.fr/bitstream/handle/2042/37512/02-1999-t0814ID1050.pdf


Other genes implicated (Data extracted from papers in the Atlas) [ 4 ]

Genes IGH IGH IGL TP53

Translocations implicated (Data extracted from papers in the Atlas)

 t(2;8)(p12;q24) IGK/MYC
 t(8;14)(q24;q32) IGH/MYC
 t(8;22)(q24;q11) IGL/MYC

External links

Mitelman databaset(2;8)(p12;q24) [Case List]    t(2;8)(p12;q24) [Association List] Mitelman database (CGAP - NCBI)
Mitelman databaset(8;14)(q24;q32) [Case List]    t(8;14)(q24;q32) [Association List] Mitelman database (CGAP - NCBI)
Mitelman databaset(8;22)(q24;q11) [Case List]    t(8;22)(q24;q11) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Other databasec-MYC / IGH t(8;14) (Bari)
Disease databaset(8;14)(q24;q32) IGH/MYC
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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