Soft Tissues: Inflammatory myofibroblastic tumor with t(1;2)(q21;p23) TPM3/ALK
2001-08-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
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
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 3)
Location
1q21.3
Protein description
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 description
1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor
Result of the chromosomal anomaly
Description
5 TPM3 - 3 ALK
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
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34727172 | 2022 | ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition. | 79 |
| 28659337 | 2017 | Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene. | 48 |
| 10702393 | 2000 | ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35). | 48 |
| 26892443 | 2016 | The landscape of fusion transcripts in spitzoid melanoma and biologically indeterminate spitzoid tumors by RNA sequencing. | 42 |
| 10934142 | 2000 | TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. | 40 |
| 37787425 | 2024 | A cutaneous epithelioid vascular tumor harboring a TPM3::ALK fusion. | 33 |
| 16651537 | 2006 | Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins. | 30 |
| 27874193 | 2017 | ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma. | 24 |
| 27742657 | 2016 | Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib. | 20 |
| 32102128 | 2020 | Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion. | 15 |
| 33091968 | 2021 | A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation. | 8 |
| 31687467 | 2019 | Corresponding anaplastic lymphoma kinase-tropomyosin 3 (ALK-TPM3) fusion in a patient with a primary cutaneous anaplastic large-cell lymphoma and a Spitz nevus. | 6 |
| 36370168 | 2023 | ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature. | 0 |
| 25596129 | 2015 | Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3. | 0 |
| 20223922 | 2010 | Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia. | 0 |
| 10216106 | 1999 | A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. | 0 |
| 38279625 | 2024 | Variant ALK-fusion positive anaplastic large cell lymphoma (ALCL): A population-based paediatric study of the NHL-BFM study group. | 0 |
| 17276053 | 2007 | TPM3-ALK expression induces changes in cytoskeleton organisation and confers higher metastatic capacities than other ALK fusion proteins. | 0 |
| 17660712 | 2007 | Development of a conditional bioluminescent transplant model for TPM3-ALK-induced tumorigenesis as a tool to validate ALK-dependent cancer targeted therapy. | 0 |
| 28181950 | 2017 | Clinicopathologic and Molecular Pathology of Collecting Duct Carcinoma and Related Renal Cell Carcinomas. | 0 |
| 38266918 | 2024 | Molecular Screening in Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: Anaplastic Lymphoma Kinase Analysis, Next-Generation Sequencing Fusion Gene Detection, and T-Cell Receptor Immunoprofiling. | 0 |
| 26773439 | 2016 | ALK-rearranged renal cell carcinomas in children. | 0 |
| 17720243 | 2008 | Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma. | 0 |
| 27450657 | 2016 | TFE3-positive renal cell carcinomas are not always Xp11 translocation carcinomas: Report of a case with a TPM3-ALK translocation. | 0 |
| 10994999 | 2000 | Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. | 0 |
| 15764578 | 2004 | Low-grade sarcomas with CD34-positive fibroblasts and low-grade myofibroblastic sarcomas. | 0 |
| 15208656 | 2004 | Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells. | 0 |
| 19545284 | 2009 | Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation. | 0 |
| 10610119 | 1999 | Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma. | 0 |
| 37731064 | 2024 | Novel gene fusion discovery in Spitz tumours and its relevance in diagnostics. | 0 |
| 22591683 | 2012 | ALK-positive anaplastic large cell lymphoma with TPM3-ALK translocation. | 0 |
| 28199742 | 2017 | Genetic analysis and clinicopathological features of ALK-rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review. | 0 |
| 21778999 | 2011 | Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas. | 0 |
| 34001695 | 2021 | Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck: Highlighting a Novel Fusion and Potential Diagnostic Pitfall. | 0 |
| 17063337 | 2007 | A case of an inflammatory myofibroblastic tumor in the lung which expressed TPM3-ALK gene fusion. | 0 |
| 12787312 | 2003 | Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype. | 0 |
| 14631806 | 2003 | [Anaplastic large-cell lymphoma: review]. | 0 |
| 20870660 | 2010 | Malignant high-grade histological transformation of inflammatory myofibroblastic tumour associated with amplification of TPM3-ALK. | 0 |
| 16984614 | 2006 | Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene. | 0 |
| 22252991 | 2012 | Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method. | 0 |
| 18660380 | 2008 | ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy. | 0 |
| 39103263 | 2024 | [ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases]. | 0 |
| 10807789 | 2000 | 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). | 0 |
| 25416234 | 2015 | Aggressive transformation of anaplastic large cell lymphoma with increased number of ALK-translocated chromosomes. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10994999 | 2000 | Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. | Drexler HG et al |
| 10383129 | 1999 | Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. | Griffin CA et al |
| 10934137 | 2000 | Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common oncogenic mechanisms. | Ladanyi M et al |
| 10216106 | 1999 | A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. | Lamant L et al |
| 10934142 | 2000 | TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. | Lawrence B et al |
| 11380391 | 2001 | Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma. | Morris SW et al |
| 10610119 | 1999 | Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma. | Siebert R et al |
| 11090048 | 2000 | CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. | Stein H et al |
Citation
Jean-Loup Huret
Soft Tissues: Inflammatory myofibroblastic tumor with t(1;2)(q21;p23) TPM3/ALK
Atlas Genet Cytogenet Oncol Haematol. 2001-08-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5129/soft-tissues-inflammatory-myofibroblastic-tumor-with-t(1
