What is the role of genetic studies in the diagnosis of primitive neuroectodermal tumor of the thoracopulmonary region (PNET)?

Updated: Dec 25, 2019
  • Author: Joseph F Tomashefski, Jr, MD; more...
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Answer

A signature gene fusion product EWS/FLI1 results from a chromosomal translocation t(11;22)(q24;q12) and is found in about 95% of PNET/EWS cases, including Askin tumor. The second most common EWS/ETS translocation, which occurs in about 5% of tumors, is t(12;22)(q22;q12), which leads to the fusion product EWS/ERG. Other translocations that lead to fusion of EWS with other genes in the ETS family of transcription factors occur in fewer than 1% of cases.

Fusion genes involving EWS/ETS are considered to be specific markers for tumors in the PNET/EWS family and are an important tool in the diagnosis of these tumors. [17, 29] The EWS/ETS fusion proteins appear to act on the expression of target genes in a sequence-specific manner that is determined by the ETS component coming under the control of the EWS component. Considered to be an oncogene, EWS/FLI1 has been shown not only to inhibit tissue specific differentiation but also to promote the Ewing-specific neuroectodermal differentiation seen in these tumors. [29]

Pathology of nonmesothelial cancers of the pleura. Pathology of nonmesothelial cancers of the pleura. A: Partial karyotype of the t(11;22)(q24;q12) translocation seen in Ewing sarcoma. Arrowheads identify the translocation breakpoints in the derivative chromosomes 11 and 22. B: Two interphase nuclei from a fluorescent in situ hybridization (FISH) assay, using an Ewing sarcoma breakpoint region 1 (EWSR1) break-apart probe set. The lower left nucleus has a normal signal pattern with two intact EWSR1 signals (yellow). The upper right nucleus has one intact EWSR1 signal identifying the normal chromosome 11 and individual green and red signals (arrows) which identify the derivative chromosomes 11 and 22, respectively.

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