t(2;22)(p23;q11.2)

Clinics and Pathology

Disease	Translocations involving 2p23 are found in more than half cases of anaplasic large cell lymphoma (ALCL), a high grade non Hodgkin lymphoma (NHL). They involve ALK, and are therefore called ALK+ ALCL. The most frequent ALK+ ALCL being the the t(2;5)(p23;q35) with NPM1 -ALK fusion protein, which localises both in the cytoplasm and in the nucleus. The t(2;22)(p23;Q11.2) is very rare, and, like other t(2;Var) involving various partners and ALK, the fusion protein has a cytoplasmic localization; they are therefore called "cytoplasm only" ALK+ ALCL. However, in case of a t(2;22) the localization is restricted to granules (vesicles) in the cytoplasm.
Phenotype / cell stem origin	CD30+; ALK+
Clinics	found in 1 case ( a 3 yr old girl in complete remission 1yr after end of treatment), perhaps 2 (a 52 yr old man).

Genes involved and Proteins

Gene Name	ALK
Location	2p23
Protein	1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor

Gene Name	CLTCL1
Location	22q11.2
Protein	1640 amino acids, 187 kDa; component of the coat of vesicles originated from the plasma membrane or the golgi

Result of the chromosomal anomaly

Hybrid gene

Description	5' CLTCL1 - 3' ALK

Fusion Protein

Description	2197 amino acids, 248-250 kDa; 1634 (nearly all the CLTCL1 protein) N-term amino acids from CLTCL1, fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain).
Oncogenesis	constitutive autophosphorylation

External links

Other database	t(2;22)(p23;q11.2)	Mitelman database (CGAP - NCBI)
Other database	t(2;22)(p23;q11.2)	CancerChromosomes (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

Characterization of a second human clathrin heavy chain polypeptide gene (CLH-22) from chromosome 22q11.

Kedra D, Peyrard M, Fransson I, Collins JE, Dunham I, Roe BA, Dumanski JP

Human molecular genetics. 1996 ; 5 (5) : 625-631.

PMID 8733129

Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like).

Touriol C, Greenland C, Lamant L, Pulford K, Bernard F, Rousset T, Mason DY, Delsol G

Blood. 2000 ; 95 (10) : 3204-3207.

PMID 10807789

CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.

Stein H, Foss HD, Dˆºrkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B

Blood. 2000 ; 96 (12) : 3681-3695.

PMID 11090048

Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.

Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (9) : 1533-1559.

PMID 10994999

Anaplastic large cell lymphomas, Primary systemic (T/Null cell type).

Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe E

World Health Organization (WHO) Classification of Tumors..

Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.

Morris SW, Xue L, Ma Z, Kinney MC

British journal of haematology. 2001 ; 113 (2) : 275-295.

PMID 11380391

Contributor(s)

Written	08-2001	Jean-Loup Huret

Citation

This paper should be referenced as such :

Huret JL . t(2;22)(p23;q11.2). Atlas Genet Cytogenet Oncol Haematol. August 2001 . URL : http://AtlasGeneticsOncology.org/Genes/t0222ID1220.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 16:32:49 2008

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