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

Highly cited references

Pubmed IDYearTitleCitations
263736762015MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.57
243361562014Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.43
168151052006Myc translocations in B cell and plasma cell neoplasms.42
163548392005Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations.37
241184982014MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations.29
229156502012IgH partner breakpoint sequences provide evidence that AID initiates t(11;14) and t(8;14) chromosomal breaks in mantle cell and Burkitt lymphomas.28
237757152013A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma.26
98657131998High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies.24
158438272005Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations.23
163274382005Adult B-cell lymphomas with burkitt-like morphology are phenotypically and genotypically heterogeneous with aggressive clinical behavior.21
312217832020Microhomology-mediated end joining drives complex rearrangements and overexpression of MYC and PVT1 in multiple myeloma.20
124810062002Mantle cell lymphoma with 8q24 chromosomal abnormalities: a report of 5 cases with blastoid features.20
213192572011Identification of IGHCδ-BACH2 fusion transcripts resulting from cryptic chromosomal rearrangements of 14q32 with 6q15 in aggressive B-cell lymphoma/leukemia.18
237959462013MYC status determination in aggressive B-cell lymphoma: the impact of FISH probe selection.16
161409302005Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice.14
159880162005Sites that direct nuclear compartmentalization are near the 5' end of the mouse immunoglobulin heavy-chain locus.14
299037642018Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements.13
286342242017IGH/MYC Translocation Associates with BRCA2 Deficiency and Synthetic Lethality to PARP1 Inhibitors.13
211206442010Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL.13
168886152006Novel FISH probes designed to detect IGK-MYC and IGL-MYC rearrangements in B-cell lineage malignancy identify a new breakpoint cluster region designated BVR2.13
254821992014Nucleolar tethering mediates pairing between the IgH and Myc loci.12
229581762012Plasmablastic lymphoma of the elderly: a clinicopathological comparison with age-related Epstein-Barr virus-associated B cell lymphoproliferative disorder.12
291323232017Integrative microRNA and mRNA deep-sequencing expression profiling in endemic Burkitt lymphoma.11
158524722005Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas.11
203030182010Detection of cryptic and variant IGH-MYC rearrangements in high-grade non-Hodgkin's lymphoma by fluorescence in situ hybridization: implications for cytogenetic testing.10
174057442007AIDS-related plasmablastic lymphoma of the oral cavity associated with an IGH/MYC translocation--treatment with autologous stem-cell transplantation in a patient with severe haemophilia-A.9
196537142009Chromosomal 3 and 8 status within hepatic metastasis of uveal melanoma.8
193369592009CD20-negative CD138-positive leukemic large cell lymphoma with plasmablastic differentiation with an IgH/MYC translocation in an HIV-positive patient.7
227264972012Sporadic Burkitt lymphomas of children and adolescents in Chinese: a clinicopathological study of 43 cases.6
194544962009Identification of the gene encoding cyclin E1 (CCNE1) as a novel IGH translocation partner in t(14;19)(q32;q12) in diffuse large B-cell lymphoma.6
291120162018B Lymphoblastic Leukemia/Lymphoma With Burkitt-like Morphology and IGH/MYC Rearrangement: Report of 3 Cases in Adult Patients.5
272179702016Validation of break-apart and fusion MYC probes using a digital fluorescence in situ hybridization capture and imaging system.5
275665742016Differential IgM expression distinguishes two types of pediatric Burkitt lymphoma in mouse and human.5
233076012013Double-hit myeloma with IGH/MYC and IGH/CCND1 translocations.5
207997672010Primary bilateral Burkitt lymphoma of the lactating breast: a case report and review of the literature.5
26452211989Reversion of tumorigenicity and decreased agarose clonability after EBV conversion of an IgH/myc translocation-carrying BL line.5
311603602019Elucidating a false-negative MYC break-apart fluorescence in situ hybridization probe study by next-generation sequencing in a patient with high-grade B-cell lymphoma with IGH/MYC and IGH/BCL2 rearrangements.4
210808892010A case of plasmablastic lymphoma harbouring an IgH/MYC translocation in a HIV negative individual.4
176395842007In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3' regulatory region induces MYC expression at the immature stage of B cell development.4
117224122001Blastic mantle cell lymphoma associated with Burkitt-type translocation and hypodiploidy.4
317057722020Molecular characteristics of terminal deoxynucleotidyl transferase negative precursor B-cell phenotype Burkitt leukemia with IGH-MYC rearrangement.3
296299472019Identification of "Double Hit" Lymphomas Using Updated WHO Criteria: Insights From Routine MYC Immunohistochemistry in 272 Consecutive Cases of Aggressive B-Cell Lymphomas.3
3034964720183'Igh enhancers hs3b/hs4 are dispensable for Myc deregulation in mouse plasmacytomas with T(12;15) translocations.3
283882792017Investigation of AID, Dicer, and Drosha Expressions in Patients with Chronic Lymphocytic Leukemia.3
223898852012A case of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma in a Korean child.3
186480002008Genetic and environmental cofactors of Myc translocations in plasma cell tumor development in mice.3
157510442005Extraosseous IL-6 transgenic mouse plasmacytoma sometimes lacks Myc-activating chromosomal translocation.3
253811332015A rare case of IGH/MYC and IGH/BCL2 double hit primary plasma cell leukemia.2
246689462014Conventional and molecular cytogenetic characterization of Burkitt lymphoma with bone marrow involvement in Brazilian children and adolescents.2
220182722011A novel five-way translocation, t(3;9;13;8;14)(q27;p13;q32;q24;q32), with concurrent MYC and BCL6 rearrangements in a primary bone marrow B-cell lymphoma.2
166161072006Burkitt t(8;14)(q24;q32) and cryptic deletion in a CLL patient: report of a case and review of literature.2
152913672004Burkitt's lymphoma of the stomach: a case report with molecular cytogenetic analysis.2
92909471997Immunoglobulin/Myc recombinations in murine Peyer's patch follicles.2
344727202022Genetic features of precursor B-cell phenotype Burkitt leukemia with IGH-MYC rearrangement.1
350243322022Anaplastic multiple myeloma with MYC rearrangement.1
333395352020Double-hit lymphoma of the male breast: a case report.1
318728612020Comparison Between Integrated Genomic DNA/RNA Profiling and Fluorescence In Situ Hybridization in the Detection of MYC, BCL-2, and BCL-6 Gene Rearrangements in Large B-Cell Lymphomas.1
311721912019Histiocytic Sarcoma Following B-Lymphoblastic Leukemia/Lymphoma.1
309830442019The accuracy of diagnosing Burkitt lymphoma in serous effusion specimen: A cytological-histological correlation with ancillary studies.1
309634742019Double-hit pancreatic B-lymphoblastic lymphoma with a variant translocation t(2;18)(p11;q21).1
265490902015Primary Burkitt's lymphoma of the breast without Epstein-Barr virus infection: A case report and literature review.1
255365682014MYC gene rearrangements detected by interphase fluorescence in situ hybridization in diffuse large B-cell lymphomas.1
204538902010Genetic reporter system for oncogenic Igh-Myc translocations in mice.1
121397452002Philadelphia chromosome-positive mature B-cell (Burkitt cell) leukaemia.1
355630172022Enhancer RNA AL928768.3 from the IGH Locus Regulates MYC Expression and Controls the Proliferation and Chemoresistance of Burkitt Lymphoma Cells with IGH/MYC Translocation.0
345217522021DNA damage-induced phosphorylation of CtIP at a conserved ATM/ATR site T855 promotes lymphomagenesis in mice.0
357660672022Looking for the truth: an IGH-MYC+ lymphoid neoplasm with immature B-cell phenotype (CD34 positivity) successfully treated with Burkitt lymphoma protocol.0
348687692021Adult Nodal Burkitt Lymphoma Forming Nodular Architectures.0
333813292020Double-Hit Primary Plasma Cell Leukemia with IGH/MYC and IGH/CCND1 Translocations.0
318317192019Molecular Cytogenetic Characterization of a Three-way t(8;14;22)(q24;q32;q11.2) with Involvement of MYC/IGH/IGL in a Case of a Diffuse Large B-cell Lymphoma (DLBCL).0
298821662018Co-fuse: a new class discovery analysis tool to identify and prioritize recurrent fusion genes from RNA-sequencing data.0
300129202018Transformation of double-hit follicular lymphoma to plasmablastic lymphoma: a partial role of MYC gene rearrangement.0
316950022019[Aggressive B-cell lymphoma with IGH/MYC, IGH/BCL2, and IGH/CCND1 translocations].0
285151002017Detection of Chromosomal Translocation in Hematologic Malignancies by a Novel DNA-Based Looped Ligation Assay (LOLA).0
275123412016Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas.0
259481772015[Cytogenetic characteristics of 163 children with acute lymphoblastic leukemia].0
230495642012Burkitt lymphoma presenting as unilateral deafness in an immunocompetent patient.0
178027972007[Detection of translocations diagnostic for Berkitt's lymphoma by fluorescent in situ hybridization on histological sections of paraffin blocks].0
83143301994Three exceptional IgH/myc-translocation-carrying rat immunocytomas have breakpoints 50 to 80 kb 5' of c-myc.0
19063441991Transcriptional deregulation of myc in IgH/myc 6;7 translocation carrying rat immunocytomas.0

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(8;14)(q24;q32)

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