| Entity | Anaplasic large cell lymphoma (ALCL) with t(2;17)(p23;q23) --> ALK - CLTC |
| Disease | ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); belong to the "cytoplasmic ALK+" subset. |
| Prognosis | Although presenting as a high grade tumour, a 80% five yr survival is associated with this anomaly |
| Hybrid/Mutated Gene | 5' CLTC - 3' ALK |
| Abnormal Protein | NH2 CLTC - COOH ALK |
| | |
| Entity | Inflammatory myofibroblastic tumors with t(2;17)(p23;q23) |
| Note | In these tumors, the fusion point in CLTC is identical, being at amino acid 1634 (corresponding to the 3' end of exon 31 of CLTC), such that almost all of CLTC is included in the fusion protein, including its trimerization domain . As a fusion partner, CLTC has been postulated to provide CLTC-ALK with deregulated expression driven by its constitutively activated promoter and constitutive oligomerization of the chimeric protein via the CLTC multimerization domains normally used for clathrin coat assembly. Since ALK is a tyrosine kinase that is activated by cross-phosphorylation following ligand binding, CLTC-ALK-induced oligomerization may result in a constitutively activated ALK tyrosine kinase domain. In this sense, CLTC is likely to function in CLTC-ALK as other prototypical "dimerizing translocation partners" in fusions involving tyrosine kinase genes. |
| Disease | rare soft tissue tumour found in children and young adults |
| Prognosis | good prognosis |
| Hybrid/Mutated Gene | 5' CLTC - 3' ALK |
| | |
| Entity | Xp11 renal translocation carcinoma with t(X;17)(p11;q23) |
| Note | In the CLTC-TFE3 fusion, the fusion point on CLTC is at amino acid 932 (corresponding to the end of exon 17), thereby excluding the CLTC trimerization domain from the predicted fusion protein. As in other TFE3 gene fusions, the nuclear localization and DNA binding domains of TFE3 are retained in CLTC-TFE3. Based on these features and existing data on other TFE3 fusion proteins, CLTC-TFE3 may act as an aberrant transcription factor, with the CLTC promoter driving constitutive expression. |
| Disease | rare renal carcinoma (single case report) |
| Prognosis | Unknown prognosis |
| Hybrid/Mutated Gene | 5' CLTC 3'TFE3 |
| | |
| Structural domains of clathrin heavy chains. |
| Kirchhausen T, Harrison SC |
| The Journal of cell biology. 1984 ; 99 (5) : 1725-1734. |
| PMID 6386825 |
| |
| Clathrin heavy chain: molecular cloning and complete primary structure. |
| Kirchhausen T, Harrison SC, Chow EP, Mattaliano RJ, Ramachandran KL, Smart J, Brosius J |
| Proceedings of the National Academy of Sciences of the United States of America. 1987 ; 84 (24) : 8805-8809. |
| PMID 3480512 |
| |
| Human clathrin heavy chain (CLTC): partial molecular cloning, expression, and mapping of the gene to human chromosome 17q11-qter. |
| Dodge GR, Kovalszky I, McBride OW, Yi HF, Chu ML, Saitta B, Stokes DG, Iozzo RV |
| Genomics. 1991 ; 11 (1) : 174-178. |
| PMID 1765375 |
| |
| Clathrin-coated vesicle formation and protein sorting: an integrated process. |
| Schmid SL |
| Annual review of biochemistry. 1997 ; 66 : 511-548. |
| PMID 9242916 |
| |
| Clathrin self-assembly is mediated by a tandemly repeated superhelix. |
| Ybe JA, Brodsky FM, Hofmann K, Lin K, Liu SH, Chen L, Earnest TN, Fletterick RJ, Hwang PK |
| Nature. 1999 ; 399 (6734) : 371-375. |
| PMID 10360576 |
| |
| Clathrin. |
| Kirchhausen T |
| Annual review of biochemistry. 2000 ; 69 : 699-727. |
| PMID 10966473 |
| |
| Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. |
| Bridge JA, Kanamori M, Ma Z, Pickering D, Hill DA, Lydiatt W, Lui MY, Colleoni GW, Antonescu CR, Ladanyi M, Morris SW |
| The American journal of pathology. 2001 ; 159 (2) : 411-415. |
| PMID 11485898 |
| |
| Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor. |
| Cools J, Wlodarska I, Somers R, Mentens N, Pedeutour F, Maes B, De Wolf-Peeters C, Pauwels P, Hagemeijer A, Marynen P |
| Genes, chromosomes & cancer. 2002 ; 34 (4) : 354-362. |
| PMID 12112524 |
| |
| A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). |
| Argani P, Lui MY, Couturier J, Bouvier R, Fournet JC, Ladanyi M |
| Oncogene. 2003 ; 22 (34) : 5374-5378. |
| PMID 12917640 |
| |
| Written | 08-2001 | Jean-Loup Huret |
| | Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| Updated | 08-2003 | Jean-Loup Huret, Sylvie Senon |
| | Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| Updated | 04-2005 | Pedram Argani, Marc Ladanyi |
| | The Johns Hopkins Hospital/ Surgical Pathology Weinberg Building, Room 2242, 4O1 N. Broadway, Baltimore, MD 21231-2410, USA |
