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X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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

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

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

Identity

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 the Burkitt lymphoma
Phenotype / cell stem origin B-cell malignant hemopathies
Epidemiology of the lymphoma : the translocation is present in both the endemic African Burkitt lymphoma and in the non endemic tumor type (Europe, America, Japan); the L3-ALL represents only 2% of ALLs and is closer to a leukemic stage of a lymphoma than to other ALL types
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 c-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, especially : structural rearrangements of the long arm of chromosome 1 (30% cases) resulting in a partial trisomy 1q, rearrangements of 13q34 (15% cases); a t(1;13)(q23;q34) has been described
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 oncogene C-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 (C-MYC locus)
Gene Name C-MYC
Location 8q24
 
Dna / Rna the human C-MYC oncogene is the cellular homologue of an avian retrovirus; in vertebrates, it belongs to a small gene family with closely related members (C-MYC, N-MYC, L-MYC); C-MYC has three exons; two promoters P1 and P2 control the C-MYC transcription; the choice of the promoter depends on the myc protein level. P2 promoter is considered as the most active promoter, generating a 2.25 kb transcript, whereas P1 promoter enrates a 2.4 kb transcript; the main part of 5' first exon corresponds to an untranslated region, MYC1 translation starting at a CUG codon near its 3'end, having 14 additional N-terminal amino-acids compared with MYC2 translation site localized 5' near the second exon beginning
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 Immunoglobulin genes : IGH, IGK, IGL
Location located in 14q32, 2p12 and 22q11 respectively

Result of the chromosomal anomaly

Hybrid gene
Note no hybrid gene but the translocation of C-MYC close to enhancers constitutively active in this specific cell lineage
Description C- 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 C-MYC with the heavy chain immunogloulin locus : 8q24 is close to the 5' extremity of C-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 C-MYC or within C-MYC; the 14q32 breakpoint region is mainly located in the constant region, very close within the switch or joining regions; C-MYC juxtaposed to the immunoglobin constant regions and enhancer is overexpressed, shutting down the normal remaining C-MYC; in both t(2;8) and t(8;22), the breakpoint is in 3' of or distal to the C-MYC gene which always remains on der(8); the rearrangement with respectively Igk or Igl and C-MYC is head-to-tail.
  
Fusion Protein
Note the protein c-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 c-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

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

Genes IGH IGH IGL

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 database Mitelman database (CGAP - NCBI)
t(2;8)(p12;q24) - Mitelman database (CGAP - NCBI)
t(8;14)(q24;q32) - Mitelman database (CGAP - NCBI)
t(8;22)(q24;q11) - Mitelman database (CGAP - NCBI)
Other databasec-MYC / IGH t(8;14) (Bari)

Bibliography

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
 
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
 
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, Mˆºller-Hermelink K, Feller A, Heinz R
Blood. 1999 ; 94 (9) : 3114-3120.
PMID 10556197
 
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
 
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Contributor(s)

Written02-1999Chrystèle Bilhou-Nabera

Citation

This paper should be referenced as such :
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.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Anomalies/t0814ID1050.html

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