t(1;2)(q25;p23)

Clinics and Pathology

Disease	Inflammatory myofibroblastic tumors
Clinics	rare soft tissue tumour found in children and young adults
Pathology	spindle cell proliferation with myofibroblastic differenciation and an inflammatory infiltrate
Prognosis	low malignant potential and good prognosis

Disease	Anaplasic large cell lymphoma: 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(1;2)(q25;p23) 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.
Epidemiology	a very few (four) cases known so far
Clinics	ALK+ ALCL without the t(2;5) (so called cytoplasmic only ALK cases) show clinical features similar to those of classical ALK+ ALCL: young age, male predominance, presentation with advanced disease, systemic symptoms, frequent involvement of extranodal sites, and a good prognosis. Nothing in particular is known concerning t(1;2) cases, as cases are not documented.
Cytogenetics	complex karyotypes and/or hidden translocation in the 2 cases with cytogenetic data; FISH analyses are essential

Genes involved and Proteins

Gene Name	TPM3 (tropomyosin alpha chain)
Location	1q25
Protein	284 amino acids, 33 kDa; coiled coil structure; role in Calcium dependant actin-myosin interaction

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' TPM3 - 3' ALK
Fusion Protein
Description	104 kDa ; 221 (?) N-term amino acids from TPM3 fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein.
Expression Localisation	cytoplasmic localisation (in contrast with the t(2;5)(p23;q35) with NPM1-ALK, which localizes both in the cytoplasm and in the nucleus).
Oncogenesis	TPM3-ALK is contituvely activated

Bibliography

A New Fusion Gene TPM3-ALK in Anaplastic Large Cell Lymphoma Created by a (1;2)(q25;p23) Translocation.

Lamant L, Dastugue N, Pulford K, Delsol G, MariamÈ B.

Blood 1999; 93: 3088-3095.

PMID 10216106

Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large cell lymphoma.

Siebert R, Gest S, Harder L, Steinemann D, Grote W, Schlegelberger B, Tiemann M, Wlodarska I, Schemmel V.

Blood 1999; 94: 3614-3617.

PMID 10610119

Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.

Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ.

Cancer Res 1999, 59: 2776-2780.

PMID 10383129

Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common oncogen,ic mechanims?

Ladanyi M.

Am J Pathol 2000; 157: 341-345.

PMID 10934137

TPM3-ALK and TPM4-ALK oncogenes in inflamatory myofibroblastic tumors.

Lawrence B, Perez-Atayde A, Hibbard MK, Rubin BP, Dal Cin P, Pinkus GS, Xiao S, Yi ES, Fletcher CDM, Fletcher JA.

Am J Pathol 2000; 157: 377-384.

PMID 10934142

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

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

Blood 2000; 96: 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 2000; 14: 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. Pathology and Genetics of tumours of Haematopoietic and Lymphoid Tissues . 2001 pp 230-235.

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

Morris SW, Xue L, Ma Z, Kinney MC.

Br J Haematol 2001; 113: 275-295.

PMID 21275125

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Contributor(s)

Written	08-2001	Jean-Loup Huret

Citation

This paper should be referenced as such :

Huret JL . t(1;2)(q25;p23). Atlas Genet Cytogenet Oncol Haematol. August 2001 . URL : http://AtlasGeneticsOncology.org/Tumors/t0102ID5129.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Apr 17 14:15:03 2008

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