t(X;2)(q11;p23)

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. In translocations other than the t(2;5), i.e. in 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(X;2) the localization is restricted to the membrane.The t(X;22)(q11;p23) is very rare.
Phenotype / cell stem origin	CD30+; ALK+
Clinics	only 1 case to date: a 18 yr old man
Prognosis	unknown: the patient achieved remission, but died of an unrelated cause

Genes involved and Proteins

Gene Name	MSN
Location	Xq11
Protein	576 amino acids, 75 kDa; cytoskeleton protein; binds to the plasma membrane and interacts with actin.

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

Result of the chromosomal anomaly

Hybrid gene

Description	5' MSN - 3' ALK. The breakpoint in ALK is different (17 bp downstream) from that observed in NPM1-ALK and other hybrid genes.

Fusion Protein

Description	1005 amino acids, 125 kDa; 448 N-term amino acid from MSN, containing the band 4.1 like domain and most of the alpha helix domain, fused to the 557 (instead of the usual 562) C-term amino acids from ALK (i.e. the cytoplasmic portion of ALK with the tyrosine kinase domain).
Expression Localisation	membrane restricted, in contrast with the t(2;5)(p23;q35) with NPM1-ALK, which localizes both in the cytoplasm and in the nucleus, and with other "variant ALK+" which have a cytoplasmic localisation.
Oncogenesis	tyrosine kinase activity.

External links

Other database	t(X;2)(q11;p23)	Mitelman database (CGAP - NCBI)
Other database	t(X;2)(q11;p23)	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

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

Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma.

Tort F, Pinyol M, Pulford K, Roncador G, Hernandez L, Nayach I, Kluin-Nelemans HC, Kluin P, Touriol C, Delsol G, Mason D, Campo E

Laboratory investigation; a journal of technical methods and pathology. 2001 ; 81 (3) : 419-426.

PMID 11310834

Contributor(s)

Written	08-2001	Jean-Loup Huret

Citation

This paper should be referenced as such :

Huret JL . t(X;2)(q11;p23). Atlas Genet Cytogenet Oncol Haematol. August 2001 . URL : http://AtlasGeneticsOncology.org/Genes/t0X02ID1216.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Dec 6 18:03:08 2008

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