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===Genetics===
===Genetics===
*The detection of a translocation involving the EWSR1 gene on chromosome 22 band q12 and any one of a number of partner chromosomes is the key feature in the diagnosis of Ewing sarcoma.
*Ewing sarcoma is the result of a [[translocation]] between chromosomes 11 and 22, which fuses the ''EWS'' gene of chromosome 22 to the ''FLI1'' gene of chromosome 11.
*The EWSR1 gene is a member of the TET family [TLS/EWS/TAF15] of RNA-binding proteins. The FLI1 gene is a member of the ETS family of DNA-binding genes.
*The ''EWSR1'' gene is a member of the ''TET'' family [''TLS''/''EWS''/''TAF15''] of RNA-binding proteins. The ''FLI1'' gene is a member of the ''ETS'' family of DNA-binding genes.
*Characteristically, the amino terminus of the EWSR1 gene is juxtaposed with the carboxy terminus of the STS family gene.
*Characteristically, the amino terminus of the ''EWSR1'' gene is juxtaposed with the carboxy terminus of the ''ETS'' family gene.
*In most cases (90%), the carboxy terminus is provided by FLI1, a member of the family of transcription factor genes located on chromosome 11 band q24.
*In most cases (90%), the carboxy terminus is provided by ''FLI1'', a member of the family of transcription factor genes located on chromosome 11 band q24.
*Other family members that may combine with the EWSR1 gene are ERG, ETV1, ETV4 (also termed E1AF), and FEV.
*Other family members that may combine with the ''EWSR1'' gene are ''ERG'', ''ETV1'', ''ETV4'' (also termed ''E1AF''), and ''FEV''.
*Rarely, TLS, another TET family member, can substitute for EWSR1.
*Rarely, ''TLS'', another ''TET'' family member, can substitute for ''EWSR1''.
*Finally, there are a few rare cases in which EWSR1 has translocated with partners that are not members of the ETS family of oncogenes. The significance of these alternate partners is not known.
*Besides these consistent aberrations involving the EWSR1 gene at 22q12, additional numerical and structural aberrations have been observed in Ewing sarcoma, including gains of chromosomes 2, 5, 8, 9, 12, and 15; the nonreciprocal translocation t(1;16)(q12;q11.2); and deletions on the short arm of chromosome 6. Trisomy 20 may be associated with a more aggressive subset of Ewing sarcoma.
*These translocations can all be found with standard cytogenetic analysis. A more rapid analysis looking for a break apart of the EWS gene is now frequently done to confirm the diagnosis of Ewing sarcoma molecularly. This test result must be considered with caution, however. Ewing sarcomas that utilize the TLS translocations will have negative tests because the EWSR1 gene is not translocated in those cases. In addition, other small round tumors also contain translocations of different ETS family members with EWSR1, such as desmoplastic small round tumor, clear cell sarcoma, extraskeletal myxoid chondrosarcoma, and myxoid liposarcoma, all of which may be positive with a EWSfluorescence in situ hybridization split apart probe.
 
Small round blue cell tumors of bone and soft tissue that are histologically similar to Ewing sarcoma but do not have rearrangements of the EWSR1 gene have been analyzed and translocations have been identified. These include BCOR-CCNB3, CIC-DUX4, and CIC-FOX4. The molecular profile of these tumors is different from the profile of EWS-FLI1 translocated Ewing sarcoma, and limited evidence suggests that they have a different clinical behavior.
 
* Ewing's sarcoma is the result of a [[translocation]] between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11. This abnormal [[gene]] caused by the [[translocation]] can in fact be found using DNA testing. This abnormality does not appear to be genetically linked, and it is exceedingly rare to have two cases of Ewing's Sarcoma within the same family.


==References==
==References==

Revision as of 14:19, 5 October 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Michael Maddaleni, B.S.

Pathophysiology

Microscopic pathology

Ewing sarcoma is a small round blue cell tumor with regular sized primitive appearing cells:

  • It consists of a homogeneous population of small round cells that have a high nuclear to cytoplasmic ratio.
  • The population of small round cells are arrayed in sheets.
  • There is a presence of scant cytoplasms which are pale, vacuolated, and are characterized by their faded boundaries.[1] The nuclei have intense color which make them easily visible. Mitotic activity is usually low within these cells, and cytoplasmic glycogen is also usually present.

Genetics

  • Ewing sarcoma is the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11.
  • The EWSR1 gene is a member of the TET family [TLS/EWS/TAF15] of RNA-binding proteins. The FLI1 gene is a member of the ETS family of DNA-binding genes.
  • Characteristically, the amino terminus of the EWSR1 gene is juxtaposed with the carboxy terminus of the ETS family gene.
  • In most cases (90%), the carboxy terminus is provided by FLI1, a member of the family of transcription factor genes located on chromosome 11 band q24.
  • Other family members that may combine with the EWSR1 gene are ERG, ETV1, ETV4 (also termed E1AF), and FEV.
  • Rarely, TLS, another TET family member, can substitute for EWSR1.

References

  1. ↑ Iwamoto Y (2007). "Diagnosis and treatment of Ewing's sarcoma". Japanese Journal of Clinical Oncology. 37 (2): 79–89. doi:10.1093/jjco/hyl142. PMID 17272319. Retrieved 2012-01-04. Unknown parameter |month= ignored (help)


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