Soft tissue sarcomas
Pat Price, Karol Sikora in Treatment of Cancer, 2014
Other chromosomal changes characteristic of specific sarcoma type include the reciprocal exchange t(11:22) (q24;ql2) seen in approximately 85%–90% of Ewing’s sarcoma and primitive peripheral neuro-ectodermal tumour (PNET).36–38 In this translocation, the EWS (Ewing sarcoma breakpoint region 1) gene from chromosome 22q12 is covalently linked to the erythroblast transformation-specific (ETS) family member, FLI-1 to form the EWS–FLI-1 fusion gene.39 The chimeric proteins that result from this translocation may alter transcription of a number of genes including upregulation of the transcription factor Gli1 that promotes the oncogenic potential of the Hedgehog pathway.39–41 A less common translocation t(21;22)(q22;q12) has also been identified and links EWS to a different ETS family member, ERG (ETS-related gene).42 Myxoid and round cell subtypes of liposarcomas display a reciprocal translocation t(12;16) (q13;p11).43,44 In this translocation, the CHOP (induced by DNA damage) gene is inserted adjacent to a novel gene called TLS. The fusion gene, called TLS–CHOP shows sequence homology to the Ewing’s fusion gene.43–46 It fails to induce G1/S arrest, which is one of the functions of the non-oncogenic form of CHOP (GADD153).47 Identification of the fusion gene has been used as a diagnostic aid for these subtypes of liposarcoma.45
Soft Tissue Sarcomas
Pat Price, Karol Sikora in Treatment of Cancer, 2020
Other chromosomal changes characteristic of specific sarcoma type include the reciprocal exchange t(11:22)(q24;ql2) seen in approximately 85%–90% of Ewing’s sarcoma and primitive peripheral neuro-ectodermal tumor (PNET). In this translocation, the EWS (Ewing sarcoma breakpoint region 1) gene from chromosome 22q12 is covalently linked to the erythroblast transformation-specific (ETS) family member, FLI-1, to form the EWS–FLI-1 fusion gene.15 The chimeric proteins that result from this translocation may alter transcription of a number of genes including upregulation of the transcription factor Gli1 that promotes the oncogenic potential of the Hedgehog pathway. A less common translocation t(21;22)(q22;q12) has also been identified and links EWS to a different ETS family member, ETS-related gene (ERG). Myxoid and round cell subtypes of liposarcomas display a reciprocal translocation t(12;16) (q13;p11). In this translocation, the CHOP (induced by DNA damage) gene is inserted adjacent to a novel gene called TLS. The fusion gene, called TLS–CHOP, shows sequence homology to the Ewing’s fusion gene. It fails to induce G1/S arrest, which is one of the functions of the non-oncogenic form of CHOP (GADD153). Identification of the fusion gene has been used as a diagnostic aid for these subtypes of liposarcoma.
Ewing Sarcoma
Dongyou Liu in Tumors and Cancers, 2017
Ewing sarcoma is shown to contain chromosomal translocation of EWS-ETS t(11;22) (q24;q12) (in 85% of cases), EWS-ERG t(21;22)(q22;q12) (in 10% of cases), EWS-ETV t(7;22)(p22;q12) and t(17;22)(q12;q12), and EWS-FEV t(2;22)(q35;q12), as well as TLS-ERG t(16;21)(p11;q22) and TLS-FEV t(2;16)(q35;p11). In addition, patients often harbor the Ewing sarcoma susceptibility gene (EGR2), located within the chromosome 10 susceptibility locus (10q21.3), which is regulated by the EWSR1 (Ewing sarcoma breakpoint region 1 of the TET family on chromosome 22)-FLI1 (friend leukemia insertion of the ETS family on chromosome 11) fusion oncogene via a GGAA microsatellite. Additional numerical and structural aberrations in Ewing sarcoma include gains of chromosomes 2, 5, 8, 9, 12, and 15; the nonreciprocal translocation t(1;16)(q12;q11.2); deletions on the short arm of chromosome 6; and trisomy 20. Further, STAG2 mutations are observed in 15%–20% of the cases, CDKN2A deletions in 12%–22% of cases, TP53 mutations in 6%–7% of cases, and intrachromosomal X-fusion in 4% of cases, leading to altered BCOR (encoding the BCL6 corepressor) and CCNB3 (encoding the testis-specific cyclin B3). In contrast, small, round, blue cell tumors of bone and soft tissue do not have rearrangements of the EWSR1 gene [2].
A case of nasopharyngeal clear cell carcinoma diagnosed by molecular analysis
Published in Acta Oto-Laryngologica Case Reports, 2018
Makiko Hara, Naoki Otsuki, Shungaku Yanagisawa, Norio Kokan, Hisami Fujio, Hitomi Shinomiya, Naruhiko Morita, Shigeru Hara, Hiroshi Inagaki, Ken-Ichi Nibu
Histopathologically, CCC was first described in 1994 by Milchgrub et al. as a unique entity made up of clear cells that form nests and cords in hyalinized stroma. Initially, CCC was called as hyalinizing clear cell carcinoma (HCCC) but was renamed as CCC in the new edition of WHO classification of Head and Neck in 2017. Since CCC has a wide differential diagnosis including other clear-cell containing tumors, such as epithelial–myoepithelial carcinoma, mucoepidermoid carcinoma (MEC), and myoepithelial carcinoma, it is very difficult to distinguish CCC from other clear-cell containing tumors based on the histopathological examination [1]. However, recently, consistent expression of Ewing sarcoma breakpoint region 1-activating transcription factor 1 (EWSR-ATF1) fusion protein has been reported in CCC. The EWSR1 rearrangement by fluorescence in situ hybridization (FISH) presented in 18 of 22 (82%) cases of CCC [2] suggested its potential role in the pathological diagnosis of CCC.
Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer
Published in Expert Opinion on Therapeutic Targets, 2018
Nidhi Jyotsana, Michael Heuser
Other splicing factors have been found as translocation partners in cancer. For example, a translocation t(11;22) in EWSR1 (RNA binding protein-EWS) gives rise to a dominant negative EWSR1/FLI-1 fusion protein that leads to mitotic instability to cause Ewing sarcoma. Fusion of the EWS transcript with different fusion partners (transcription activators or repressors such as WT1 or ATF-1) gives rise to different types of tumors such as EWS-WT1 in desmoplastic sarcoma with small round cells [55] and EWS-ATF-1 in malignant melanoma of soft tissues [56]. The splicing factor proline/glutamine rich protein PSF/SFPQ is fused to tyrosine kinase Abelson murine leukemia viral oncogene homolog 1 (ABL1) in acute lymphoid leukemia (ALL) [57] and to TFE3 in papillary renal cell carcinomas [58]. SRP20 is a partner of BCL6 in transformed follicular lymphomas [59].
Ewing Sarcoma Displaying Extensive Well Differentiated Neuroblastomatous Differentiation: A Case Report
Published in Fetal and Pediatric Pathology, 2023
Nil Çomunoğlu, Cem Çomunoğlu, Rahşan Özcan, Süheyla Ocak
Ewing Sarcoma (ES) was first described by Stout in 1918 and by Ewing in 1921 [1,2]. The recurrent and specific chromosomal translocation is t(11;22) with the defining Ewing sarcoma breakpoint region 1 (EWSR1) located on chromosome 22q12.2 [3–5]. Histopathologically, classic ES display sheets of uniform small round cells with round nuclei having finely granular chromatin and inconspicuous nucleoli [6]. ES has been thought to have a neuroectodermal origin [7], however, in ES prominent neural differentiation especially in the form of ganglioneuroblastoma is an unusual histopathological finding [8]. Neuroblastoma is reported to be the fourth most common malignancy of childhood [9] and differentiating neuroblastoma from round cell sarcomas, especially ES, may be problematic. This report presents a tumor with the classic EWSR1/FLI translocation characteristic of ES with extensive multiple foci of neurophil, containing embedded mature and dysplastic ganglion cells, complicating the histopathological diagnosis.
Related Knowledge Centers
- Chromosome 22
- Ewing Sarcoma
- Protein
- Gene
- Fet Protein Family
- Ews/Fli
- Ewing Family of Tumors
- Chromoplexy
- Als
- Protein–Protein Interaction