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).
Expression Localisation	cytoplasmic localization restricted to granules
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 : Sat Dec 6 18:02:20 2008

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