t(1;2)(q25;p23) TPM3/ALK

Identity

ICD-Topo	C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id	1168

Clinics and Pathology

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

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

Genes involved and Proteins

Gene Name	TPM3 (tropomyosin 3)
Location	1q21.3
Protein	284 amino acids, 33 kDa; coiled coil structure; role in Calcium dependant actin-myosin interaction

Gene Name	ALK (anaplastic lymphoma receptor tyrosine kinase)
Location	2p23.2
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

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

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..

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

Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.

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

Cancer research. 1999 ; 59 (12) : 2776-2780.

PMID 10383129

Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common oncogenic mechanisms.

Ladanyi M

The American journal of pathology. 2000 ; 157 (2) : 341-345.

PMID 10934137

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, Mariamé B

Blood. 1999 ; 93 (9) : 3088-3095.

PMID 10216106

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

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

The American journal of pathology. 2000 ; 157 (2) : 377-384.

PMID 10934142

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

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

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

Blood. 1999 ; 94 (10) : 3614-3617.

PMID 10610119

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

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

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

PMID 11090048

Citation

This paper should be referenced as such :

Huret, JL

t(1;2)(q25;p23)

Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):279-280.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Anomalies/t0102ID1168.html

Translocations implicated (Data extracted from papers in the Atlas)

	t(1;2)(q25;p23) TPM3/ALK

External links

TPM3 (1q21.3) ALK (2p23.2)

TPM3 (1q21.3) ALK (2p23.2)

Mitelman database	t(1;2)(q25;p23) [Case List]    t(1;2)(q25;p23) [Transloc-MCList] TPM3/ALK [Fusion-MCList]
arrayMap (UZH-SIB Zurich)	[select an item]
Mitelman database	TPM3/ALK [MCList]  TPM3 (1q21.3) ALK (2p23.2)
TICdb	TPM3/ALK  TPM3 (1q21.3) ALK (2p23.2)

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

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indexed on : Mon Aug 12 16:59:37 CEST 2019

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