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t(2;7)(p11;q21) IGK::CDK6

t(7;14)(q21;q32) IGH::CDK6

t(7;22)(q21;q11) IGL::CDK6

t(7;14)(q21;q11) TRA::CDK6

Written2021-02Elise Chapiro, Baptiste Gaillard, Florence Nguyen-Khac
Cytogénétique Hématologique, Service d'Hématologie Biologique, Hpital Pitié-Salpêtrière, APHP,.Sorbonne Université. Centre de Recherche des Cordeliers, INSERM UMRS_1138, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Paris, France; (EC, FNK), Laboratoire d'Hématologie, Hpital Robert Debré, Reims, France (BG)
This article is an update of :
2009-02Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Abstract Translocations involving the CDK6 gene are rare but recurrent abnormalities in mature B-cell neoplasms, mainly marginal zone lymphoma and chronic lymphocytic leukemia. Four different translocations have been described: t(2;7)(p11;q21) (the most frequent), t(7;14)(q21;q32), t(7;14)(q21;q11) and t(7;22)(q21;q11), leading to juxtaposition of the CDK6 gene with the IGK, IGH, TRA or IGL locus, respectively, and thus CDK6 overexpression.

Keywords CDK6, IGK, marginal zone lymphoma, chronic lymphocytic leukemia

(Note : for Links provided by Atlas : click)


ICD-Morpho 9823/3 Chronic lymphocytic leukaemia /small lymphocytic lymphoma
ICD-Morpho 9699/3 Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma); Nodal marginal zone lymphoma; Paediatric nodal marginal zone lymphoma
Atlas_Id 1361
  Figure 1. Translocation t(2;7)(p11;q21) and variants. Left: t(2;7)(p11;q21) IGK /CDK6. R-banding, Top: - Courtesy Karolien Beel, Peter Meeus and Lucienne Michaux (CME Leuven); Middle (R-banding) and Bottom (G-banding): - Courtesy Baptiste Gaillard (Reims), Elise Chapiro (Paris) and Audrey Bidet (Bordeaux); Center and Right: t(7;14)(q21;q11) and t(7;14)(q21;q32) - Courtesy Baptiste Gaillard (Reims), Elise Chapiro (Paris) and Audrey Bidet (Bordeaux)

Clinics and Pathology

Disease To date, t(2;7) and its variants have been documented in about 100 cases: mainly marginal zone lymphoma (sMZL) (about 2/3 of patients) and Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (~15%), but also high-grade B-cell lymphoma not otherwise specified, unclassified small B-cell lymphoma and monoclonal B-cell lymphocytosis (marginal-zone type). One case of nodal MZL, one bronchus-associated lymphoid tissue (BALT) lymphoma, and one gastric MALT (mucosa-associated lymphoid tissue) lymphoma were also reported.
Epidemiology The frequency is estimated to 0.32% of mature B-cell neoplasms (Gaillard et al., 2020).
Cytology A small proportion of prolymphocytic cells are mixed with classical marginal zone cells in about 70% of t(CDK6)+ MZL (Gaillard et al., 2020).
Pathology The expression of CD5 is frequent in t(CDK6)+ lymphomas (more than half of cases) (Gaillard et al., 2020).
Prognosis Prognosis seems good. In a series of 47 t(CDK6)+ MZL and small B-cell lymphomas, the 5-year overall survival (OS) rate was above 80%. The presence of del(17p) or a TP53 mutation does not appear to influence OS (Gaillard et al., 2020).


The great majority of t(CDK6)+ MZL and small B-cell lymphomas carry IGHV mutations. The most frequent IGHV genes identified are V3-23 and V4-59 (14% and 10% respectively). The IGHV1-02*04 gene, the most frequent allele in classical splenic MZL, is not found.
Mutations in TP53 gene are frequent (27%). No mutations in NOTCH2 (Gaillard et al., 2020).


Cytogenetics Morphological The translocation t(2;7) is described in the great majority of cases (> 90%), mainly splenic marginal zone lymphomas (sMZL) and chronic lymphocytic leukemia (CLL). Variant translocations are more frequent in CLL; t(7;22) IGL/CDK6 (reported in only one case) and t(7;14) IGH/CDK6 are restricted to CLL. The t(7;14) TRA/CDK6 has been described in four cases: two CLL and two sMZL.
  Figure 2. Top: t(2;7)(p11;q21) : FISH IGK (DC BA)(316G9) (SG) (526L16-1021F11)(SO) (2p11) - Courtesy Karolien Beel, Peter Meeus and Lucienne Michaux (CME Leuven); Second to fourth rows: - Courtesy Elise Chapiro (Paris) A and B: t(2;7)(p11;q21) A. FISH with the home-made break-apart CDK6 probe (RP11-246N14 labeled in FITC + RP11-90H9 labeled in Rhodamine). B. IGK (2p11) break-apart probe (Cytocell). C and D: t(7;14)(q21;q11) C. Home-made break-apart CDK6 probe (RP11-246N14 labeled in FITC + RP11-90H9 labeled in Rhodamine). D. TRAD (14q11) break-apart probe (Cytocell). E and F: t(7;14)(q21;q32) E. Home-made break-apart CDK6 probe (RP11-246N14 labeled in FITC + RP11-90H9 labeled in Rhodamine). F. IGH (14q32) break-apart probe Vysis (Abbott).
Cytogenetics Molecular FISH analyses revealed that the breakpoint in IGK is located in the IGKV proximal region in the majority of the patients. In one third, the breakpoint is more centromeric (in the IGKV distal region).
  Figure 3.
Additional anomalies Additional abnormalities are found in 2/3 of cases. Complex karyotypes (>3 abnormalities) are frequent (about half of cases). The most frequent additional chromosomal aberrations are: del(17p)) involving the TP53 gene, del(13q14), del(8p), trisomy 3, 8q gain, trisomy 12 and trisomy 18. Del(7q) is rare contrary to classical sMZL.

Genes involved and Proteins

Gene NameCDK6 (cyclin dependent kinase 6)
Location 7q21.2
Note Alias: PLSTIRE
Protein CDK6 is highly homologous to CDK4. CDK6 has a kinase-dependent activity in the cell cycle progression (regulation of the G1 early phase), survival, differentiation, and senescence that requires binding to D-type cyclin (CCND1, CCND2 and CCND3). CDK6 also acts as a chromatin-bound cofactor that in a kinase-independent manner induces transcription of genes regulating angiogenesis, cell cycle inhibition, stem cell activation and immune response. (for review, see Nebenfuehr et al., 2020).
Gene NameIGH (Immunoglobulin Heavy)
Location 14q32.33
Note Alias: IGHDY1, IGH@
Protein Immunoglobulin heavy chain: part of the B-cell receptor (BCR).
Gene NameIGK: (Immunoglobulin Kappa)
Location 2p11.2
Note Alias: IGK@
Protein Immunoglobulin light chain: part of the B-cell receptor (BCR)
Gene NameTRA (T Cell Receptor Alpha)
Location 14q11.2
Note Alias: TCRA, TRA@
Protein T-cell receptor alpha: part of the T-cell receptor complex
Gene NameIGL (Immunoglobulin Lambda)
Location 22q11.2
Note Alias: IGL@
Protein Immunoglobulin light chain: part of the B-cell receptor (BCR)

Result of the chromosomal anomaly

Hybrid gene
Description The translocation juxtaposes CDK6 close to IG(/TCR) enhancers which are constitutively active in B-cells. The sequencing of the t(2;7) breakpoints revealed that junction sites on 2p11 localized to the recombination signal sequences (RSS) of a gene segment belonging to the VK3 family of IGK variable genes, while the breakpoints on 7q21 mapped to an RSS-like element located approximately 0.5 kb upstream of the transcription start site of the CDK6 gene. These observations strongly suggest that the VJ or VDJ recombination machinery is involved in the formation of this translocation (Parker et al., 2013).
Fusion Protein
Oncogenesis Overexpression of CDK6 was demonstrated (Corcoran et al., 1999; Brito-Babapulle et al., 2002; Hayette et al., 2003).


New chromosomal alterations in a series of 23 splenic marginal zone lymphoma patients revealed by Spectral Karyotyping (SKY)
Baró C, Salido M, Espinet B, Astier L, Domingo A, Granada I, Millà F, Carrió A, Costa D, Luño E, Hernández JM, Campo E, Florensa L, Ferrer A, Salar A, Bellosillo B, Besses C, Serrano S, Solé F
Leuk Res 2008 May;32(5):727-36.
PMID 18023866
Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia
Brito-Babapulle V, Gruszka-Westwood AM, Platt G, Andersen CL, Elnenaei MO, Matutes E, Wotherspoon AC, Weston-Smith SG, Catovsky D
Haematologica 2002 Apr;87(4):357-62.
PMID 11940479
Clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders
Chen D, Law ME, Theis JD, Gamez JD, Caron LB, Vrana JA, Dogan A
Am J Surg Pathol 2009 May;33(5):720-9.
PMID 19145199
Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations
Corcoran MM, Mould SJ, Orchard JA, Ibbotson RE, Chapman RM, Boright AP, Platt C, Tsui LC, Scherer SW, Oscier DG
Oncogene 1999 Nov 4;18(46):6271-7.
PMID 10597225
Clinical and biological features of B-cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities
Gailllard B, Cornillet-Lefebvre P, Le QH, Maloum K, Pannetier M, Lecoq-Lafon C, Grange B, Jondreville L, Michaux L, Nadal N, Ittel A, Luquet I, Struski S, Lefebvre C, Gaillard JB, Lafage-Pochitaloff M, Balducci E, Penther D, Barin C, Collonge-Rame MA, Jimenez-Poquet M, Richebourg S, Lemaire P, Defasque S, Radford-Weiss I, Bidet A, Susin SA, Nguyen-Khac F, Chapiro E,
Br J Haematol 2020 Dec 13.
PMID 33314017
In B-cell chronic lymphocytic leukemias, 7q21 translocations lead to overexpression of the CDK6 gene
Hayette S, Tigaud I, Callet-Bauchu E, Ffrench M, Gazzo S, Wahbi K, Callanan M, Felman P, Dumontet C, Magaud JP, Rimokh R
Blood 2003 Aug 15;102(4):1549-50.
PMID 12900351
The role of CDK6 in cancer
Nebenfuehr S, Kollmann K, Sexl V
Int J Cancer 2020 Dec 1;147(11):2988-2995.
PMID 32406095
Cytogenetic studies in splenic lymphoma with villous lymphocytes
Oscier DG, Matutes E, Gardiner A, Glide S, Mould S, Brito-Babapulle V, Ellis J, Catovsky D
Br J Haematol 1993 Nov;85(3):487-91.
PMID 8136270
Molecular characterization of a t(2;7) translocation linking CDK6 to the IGK locus in CD5(-) monoclonal B-cell lymphocytosis
Parker E, Macdonald JR, Wang C
Cancer Genet 2011 May;204(5):260-4.
PMID 21665179
The prevalence of IG translocations and 7q32 deletions in splenic marginal zone lymphoma
Remstein ED, Law M, Mollejo M, Piris MA, Kurtin PJ, Dogan A
Leukemia 2008 Jun;22(6):1268-72.
PMID 17989713
Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group
Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F
Blood 2010 Sep 2;116(9):1479-88.
PMID 20479288
Karyotype analysis of B-lymphocytes transformed by Epstein-Barr virus in 21 patients with B cell chronic lymphocytic leukemia
Vahdati M, Graafland H, Emberger JM
Hum Genet 1983;63(4):327-31.
PMID 6305826
Involvement of a human endogenous retroviral sequence (THE-7) in a t(7;14)(q21;q32) chromosomal translocation associated with a B cell chronic lymphocytic leukemia
Wahbi K, Hayette S, Callanan M, Gadoux M, Charrin C, Magaud JP, Rimokh R
Leukemia 1997 Aug;11(8):1214-9.
PMID 9264372
Translocation t(2;7)(p11.2;q21.2): a rare genetic aberration associated with B-cell lymphoproliferative disorders of marginal-zone origin
Xochelli A, Baliakas P, Moore S, Sole F, Wickham N, Salido M, Athanasiadou A, Oscier D, Stamatopoulos K
Cancer Genet 2014 Jun;207(6):281-3.
PMID 25178943


This paper should be referenced as such :
Chapiro E, Gaillard B, Nguyen-Khac F
t(2;7)(p11;q21) IGK::CDK6; t(7;14)(q21;q32) IGH::CDK6; t(7;22)(q21;q11) IGL::CDK6; t(7;14)(q21;q11) TRA::CDK6;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :
History of this paper:
Huret, JL. t(2;7)(p11;q21) - t(7;14)(q21;q32) CDK6/IgH - t(7;22)(q21;q11). Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):68-69.

Translocations implicated (Data extracted from papers in the Atlas)

 t(2;7)(p11;q21) IGK/CDK6
 t(7;22)(q21;q11) IGL/CDK6

External links

IGK (14q32.33) CDK6 (7q21.2)

IGH (14q32.33) CDK6 (7q21.2)

IGL (22q11.22) CDK6 (7q21.2)

Mitelman databaset(2;7)(p11;q21)
Mitelman databaset(7;14)(q21;q32)IGH/CDK6
Mitelman databaset(7;22)(q21;q11)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9823/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9699/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseIGK::CDK6 [MCList]  IGK (14q32.33) CDK6 (7q21.2)
Mitelman databaseIGH::CDK6 [MCList]  IGH (14q32.33) CDK6 (7q21.2)
Mitelman databaseIGL::CDK6 [MCList]  IGL (22q11.22) CDK6 (7q21.2)
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indexed on : Fri Oct 8 16:36:52 CEST 2021

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