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t(2;7)(p11;q21)

t(7;14)(q21;q32) CDK6/IgH

t(7;22)(q21;q11)

Identity

Note The translocation t(7;14)(q21;q32) herein described must not be confused with the t(7;14)(q21;q32) with ERVWE1/IgH involvement, seen in chronic lymphocytic leukaemia (Wahbi et al., 1997). There is also a case of acute myeloid leukaemia with t(7;14)(q21;q32) in a female patient, with no other data (Stephenson et al., 1995).

Clinics and Pathology

Disease Chronic lymphocytic leukaemia (CLL) and splenic marginal zone lymphoma (SMZL) (Corcoran et al., 1999; Hayette et al., 2003).
Phenotype / cell stem origin Six patients, aged 52-79 years, 5 male / 1 female cases.
Prognosis Survival data was: 3 years+, 6 years+, and a case dead 16 years after diagnosis in the CLL cases; 4 years+, 5 years+, and 8 years+ in the SMZL and variants cases.

Cytogenetics

Cytogenetics Morphological Sole anomaly in two of six cases.
Additional anomalies Accompanied with +12 in two CLL cases, del(13q) in one CLL, del(7q) in one SMZL case.

Genes involved and Proteins

Gene Name CDK6
Location 7q21.2
Protein G1 phase kinase; phosphorylates RB1 but with a distinct activity from CDK4. Control of the cell cycle; blockage of differenciation (Grossel and Hinds, 2006).
Gene Name IGH
Location 14q32.33
Note IGH was involved in the one case with a t(7;14), while IGK (2p11) was involved in four cases showing a t(2;7), and IGL (22q11) in the case with a t(7;22).
Protein Immunoglobulin heavy chain (see Lefranc, 2003).

Result of the chromosomal anomaly

Hybrid gene
Description Translocation of CDK6 close to enhancers constitutively active in B- cells.
  
Fusion Protein
Note The case elsewere reported with t(7;14)(q21;q32) ERVWE1/IgH (Wahbi et al., 1997) may also involve CDK6 instead of ERVWE1, as it is known that IG enhancers may act at long distance. However, the breakpoint in this latter case was found 94 bases upstream ERVWE1. ERVWE1 is 127 kb upstream CDK6 on minus strand of the DNA (ERVWE1 is from 91 935 631 to 91 945 186, and CDK6 from 92 072 173 to 92 303 877), while the breakpoints herein reported are situated within 2 to 66 kb near CDK6, and they appear to be telomeric to CDK6.
Oncogenesis Overexpression of CDK6 was demonstrated (Hayette et al., 2003).
  

External links

Other databaset(2;7)(p11;q21) Mitelman database (CGAP - NCBI)
Other databaset(7;14)(q21;q32) CDK6/IgH Mitelman database (CGAP - NCBI)
Other databaset(7;22)(q21;q11) Mitelman database (CGAP - NCBI)

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.

Bibliography

Possible co-existence of RAS activation and monosomy 7 in the leukaemic transformation of myelodysplastic syndromes.
Stephenson J, Lizhen H, Mufti GJ.
Leuk Res. 1995 Oct;19(10):741-8.
PMID 7500652
 
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
 
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
 
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
 
IGH (Immunoglobulin Heavy).
Lefranc MP.
Atlas Genet Cytogenet Oncol Haematol. September 2003 http://AtlasGeneticsOncology.org/Genes/IgHID40.html
 
From cell cycle to differentiation: an expanding role for cdk6.
Grossel MJ, Hinds PW.
Cell Cycle. 2006 Feb;5(3):266-70. Epub 2006 Feb 6. (REVIEW)
PMID 16410727
 

Contributor(s)

Written02-2009Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Citation

This paper should be referenced as such :
Huret JL . t(2;7)(p11;q21); t(7;14)(q21;q32) CDK6/IgH; t(7;22)(q21;q11). Atlas Genet Cytogenet Oncol Haematol. February 2009 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0714q21q32ID1361.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/44666/1/02-2009-t0714q21q32ID1361.pdf   [ Bibliographic record ]

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