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t(2;12)(p12;p13) IGK/CCND2

t(12;14)(p13;q32) IGH/CCND2

t(12;22)(p13;q11) IGL/CCND2

Written2009-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 1487
Note Mantle cell lymphoma are usually associated with a t(11;14)(q13;q32), a CCND1/IgH rearrangement, and cyclin D1 overexpression.

Clinics and Pathology

Disease Mantle cell lymphoma (MCL)
Note This review does not include a case of t(2;12)(p12;p13) found in myeloid malignancy (Lai et al., 1995), a case of acute lymphoblastic leukemia with a t(12;14)(p13;q32) and IgH/ETV6 involvement (Lu et al., 2002); five cases of t(12;22)(p13;q11), not herein included either, have also been described in lymphoid malignancies, but with an unknown CCND2 status (see Mitelman database). Finally, there are a number of chronic myeloid leukemia aberrant translocations with t(12;22), which again represent other diseases.
Phenotype / cell stem origin The cases of mantle cell lymphomas with the above translocations were typical mantle cell cases, with CD5+, CD20+, CD10-, CD23- expression, except for the lack of CCND1 expression.
Epidemiology Five cases are available: 4 cases of MCL (Gesk et al., 2006; Herens et al., 2008; Wlodarska et al., 2008), and a case of chronic lymphocytic leukemia (CLL) transforming into a Richter disease (Qian et al., 1999).
Clinics The patients are in stage IV of the disease, with a nodular, or nodular/diffuse pattern. There was 3 male and 2 female patients, aged 33, 52, 65, 70, and ? years.
Prognosis Data is missing in most cases; the two patients with data on prognosis died: the patient with Richter disease, and a MCL case, who died 64 months after diagnosis.

Cytogenetics

Cytogenetics Morphological There was two cases of t(2;12), one case of cryptic t(12;14), one case of t(12;22), and one case with no metaphase.
Additional anomalies +3 was found in two cases, +21 in one case, a complex karyotype in one case, and +12 and a t(14;19)(q32;q13) in the CLL/Richter case.

Genes involved and Proteins

Note IgH, IgK, or IgL can be alternative partners of CCND2.
Gene Name CCND2
Location 12p13
Protein CCND2 promotes cell cycle progression at the G1/S start transition. Interacts with CDK4 and CDK6. CCND2 is activated through B-cell antigen receptor-induced, and CD19-induced signal transduction pathways, including the RAS/RAF/MAPK pathway, the PLC gamma pathway, and the IKK/NF-KB pathway. CCND2 is critical in B-cell development (review in Chiles, 2004).

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Overexpression of cyclin D2.
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.
Case Report The t(2;12)(p12;p13), leading to the juxtaposition of the cyclin D2 CCND2 gene with the immunoglobulin kappa locus (IGK), defines a small subset of mantle cell lymphomas lacking cyclin D1 expression

Bibliography

Regulation and function of cyclin D2 in B lymphocyte subsets.
Chiles TC.
J Immunol. 2004 Sep 1;173(5):2901-7. (Review)
PMID 15322145
 
A chromosomal translocation in cyclin D1-negative/cyclin D2-positive mantle cell lymphoma fuses the CCND2 gene to the IGK locus.
Gesk S, Klapper W, Martin-Subero JI, Nagel I, Harder L, Fu K, Bernd HW, Weisenburger DD, Parwaresch R, Siebert R.
Blood. 2006 Aug 1;108(3):1109-10.
PMID 16861358
 
Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression.
Herens C, Lambert F, Quintanilla-Martinez L, Bisig B, Deusings C, de Leval L.
Blood. 2008 Feb 1;111(3):1745-6.
PMID 18223179
 
Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations.
Lai JL, Preudhomme C, Zandecki M, Flactif M, Vanrumbeke M, Lepelley P, Wattel E, Fenaux P.
Leukemia. 1995 Mar;9(3):370-81.
PMID 7885035
 
The utility of spectral karyotyping in the cytogenetic analysis of newly diagnosed pediatric acute lymphoblastic leukemia.
Lu XY, Harris CP, Cooley L, Margolin J, Steuber PC, Sheldon M, Rao PH, Lau CC.
Leukemia. 2002 Nov;16(11):2222-7.
PMID 12399965
 
Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non-Hodgkin's lymphoma.
Qian L, Gong J, Liu J, Broome JD, Koduru PR.
Br J Haematol. 1999 Aug;106(2):477-85.
PMID 10460609
 
Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas.
Wlodarska I, Dierickx D, Vanhentenrijk V, Van Roosbroeck K, Pospisilova H, Minnei F, Verhoef G, Thomas J, Vandenberghe P, De Wolf-Peeters C.
Blood. 2008 Jun 15;111(12):5683-90.
PMID 18391076
 

Citation

This paper should be referenced as such :
Huret, JL
t(2;12)(p12;p13) - t(12;14)(p13;q32) - t(12;22)(p13;q11)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):992-993.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1214p13q32ID1487.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(12;22)(p13;q11) IGL/CCND2
 t(2;12)(p12;p13) IGK/CCND2
 t(12;14)(p13;q32) IGH/CCND2

External links

arrayMap (UZH-SIB Zurich)IGH (14q32.33) CCND2 (12p13.32)

Mitelman databaset(12;22)(p13;q11) [Case List]    t(12;22)(p13;q11) [Association List] Mitelman database (CGAP - NCBI)
Mitelman databaset(2;12)(p12;p13) [Case List]    t(2;12)(p12;p13) [Association List] Mitelman database (CGAP - NCBI)
Mitelman databaset(12;14)(p13;q32) [Case List]    t(12;14)(p13;q32) [Association List] Mitelman database (CGAP - NCBI)
arrayMap[select an item]
 
Mitelman databaseIGH/CCND2 [MCList]  IGH (14q32.33) CCND2 (12p13.32)
 
Disease databaset(2;12)(p12;p13) IGK/CCND2
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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