Fusion of the ALK Gene to the Clathrin Heavy Chain Gene, CLTC, in Inflammatory Myofibroblastic Tumor

Abstract

Inflammatory myofibroblastic tumor (IMT) is a rare, but distinctive mesenchymal neoplasm composed of fascicles of bland myofibroblasts admixed with a prominent inflammatory component. Genetic studies of IMTs have demonstrated chromosomal abnormalities of 2p23 and rearrangement of the anaplastic lymphoma kinase (ALK) gene locus. In a subset of IMTs, the ALK C-terminal kinase domain is fused with a tropomyosin N-terminal coiled-coil domain. In the current study, fusion of ALK with the clathrin heavy chain (CTLC) gene localized to 17q23 was detected in two cases of IMT. One of these cases exhibited a 2;17 translocation in addition to other karyotypic anomalies [46,XX,t(2;17)(p23;q23),add(16)(q24)].

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

“…11 Subsequently, recurrent ALK chimeric oncogenes involving diverse partner genes (RanBP2, CLTC, CARS, and others) were identified in inflammatory myofibroblastic tumors. [15][16][17][18] More recently, the ALK gene has been shown to be involved in small subsets of epithelial malignancies, including carcinomas of pulmonary, esophageal, mammary gland, and gastrointestinal origin. [19][20][21][22] To the best of our knowledge, this is the first report of a recurrent ALK locus rearrangement in a primary kidney tumor.…”

“…This probe set was used to confirm or assess for the presence of a VCL-ALK fusion in cases 1 and 2, respectively, and to further characterize the cytogenetically complex chromosomal rearrangements observed in case 1. Whole chromosome paint and centromere-specific probes for chromosomes 9 and 10 (Cytocell, Cambridge, UK and Abbott 16 Hybridization signals were assessed in 1-3 metaphase cells for each FISH probe combination (case 1) or in 200 interphase nuclei (cases 1-6); strong, well-delineated signals were independently scored by two individuals. An interphase cell specimen was interpreted as abnormal if split ALK break-apart probe signals were detected in 45% of the cells or juxtaposed VCL-ALK probe set signals were detected in 410% of cells (42 s.d.…”

“…11 Subsequently, ALK rearrangements were found in several phenotypically different hematologic neoplasms [12][13][14] and in histogenetically unrelated inflammatory myofibroblastic tumor. [15][16][17][18] Recently, ALK rearrangements and EML4-ALK and KIF5B-ALK fusions were discovered in a subset of non-small cell lung carcinomas; 19,20 proteomics reports suggested a possible TPM4-ALK fusion in esophageal carcinoma; 21,22 and an exon array profiling study demonstrated the EML4-ALK fusion in 2.5% of breast and colon cancers. 23 ALK is also activated in B5 to 35% of neuroblastomas and neuroblastoma cell lines by a different mechanism involving point mutations and/or gene locus amplifications.…”

Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder

“…4,5,7,9,[20][21][22][23][24][25][29][30][31][32] Cytogenetic and molecular analyses have demonstrated a number of ALK fusion gene partners, including RANBP2-ALK, TPM3-ALK, TPM4-ALK, CLTCALK, CARS-ALK and SEC31L1-ALK. 5,9,21,25,29,31 In the present study, ALK rearrangements were identified in 14 of 21 cases of inflammatory myofibroblastic tumor of the urinary bladder. These findings are similar to recent studies that identified ALK rearrangements by FISH in a few series of urinary bladder inflammatory myofibroblastic tumors.…”

Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature

“…[20][21][22] The favourable outcome of IMFT in the lung and bladder 23 is well known, however, and even in a wide range of anatomical sites examined, there is a low rate of local recurrence (25%) and no metastases reported (Table 3). 2,10,15 This indicates that vesical IMFT may be treated with conservative surgical excision compared to that performed with sarcomatous lesions, which may resemble IMFT clinically and radiologically.…”