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

2016-05-01   Eva van den Berg , Eva van den Berg 

1.Department of Genetics, University Medical Centre Groningen, Groningen; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands e.van.den.berg-de.ruiter@umcg.nl; Marian.Stevens-Kroef@radboudumc.nl

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 stem cell 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.
Atlas Image
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.

Cytology

ALL : L3 morphology according to the FAB classification, very occasionally L1 or L2 cytology reported.

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).
Atlas Image
t(8;14)(q24;q32) IGH/MYC G-banding and Hybridization with Vysis LSI IGH/MYC dual color probe (Abbott Molecular, US) showing fused yellow signals on der(8) and der(14) chromosomes - Courtesy Adriana Zamecnikova. Top right: The figure illustrates the translocation of the MYC gene (probe 944B18, red) to 14q32.3 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

Additional anomalies

Reported in 70% cases in Burkitt lymphoma and DLBCL, especially: t(14;18)(q32;q21) in double-hit DLBCL lymphomas, 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 v-myc myelocytomatosis viral oncogene homolog (avian)
Location
8q24.21
Dna rna description
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.
Atlas Image
Protein description
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 (Immunoglobulin Heavy)
Location
14q32.33
Note
Or other Immunoglobulin genes IGK, IGL located in 2p12 and 22q11 respectively.

Result of the Chromosomal Anomaly

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.

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

Bibliography

Pubmed IDLast YearTitleAuthors
105778571999World 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 et al
110544442000Molecular biology of Burkitt's lymphoma.Hecht JL et al
18692431991Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature.Kornblau SM et al
75236071994Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy.Longo DL et al
105561971999Clinicopathogenetic significance of chromosomal abnormalities in patients with blastic peripheral B-cell lymphoma. Kiel-Wien-Lymphoma Study Group.Schlegelberger B et al

Summary

Fusion gene

IGH/MYC , IGK/MYC , IGL/MYC

Note

The 3 translocations are variants of each other, and they share the same clinical significance.
Atlas Image
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.

Citation

Eva van den Berg ; Eva van den Berg

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. 2016-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1050/t(2;8)(p12;q24)

Historical Card

1999-02-01 t(8;14)(q24;q32) IGH/MYC
t(2;8)(p12;q24) IGK/MYC
t(8;22)(q24;q11) IGL/MYC
 by  Chrystele Bilhou-Nabera 

External Links