Methods and compositions for the diagnosis and treatment of ewing's sarcoma
Patent Number: US7939253
Executive Summary:
General Description:
Ewing's sarcoma is an aggressive and highly metastatic malignancy and it arises in and around the bones of the extremities and central skeleton, but may also arise in the soft tissues as “extraosseous Ewing's.” Ewing's sarcoma primarily affects children and young adults, predominantly those of European descent, with the highest rates of development occurring in white male adolescents.
The diagnosis of Ewing's sarcoma is typically based on histologic criteria and associated expression of EWS/FLI. The majority of the translocations code for EWS/FLI. However, a minority of translocations encode fusions that are similar, but not identical to EWS/FLI. Consequently, molecular diagnostics that test for EWS/FLI, such as quantitative PCR, miss approximately 15% of Ewing's sarcoma cases. Immunohistochemistry is a more wide-spread and readily applied technique for diagnosis. The most specific and sensitive immunohistochemical marker for Ewing's sarcoma is CD99 expression. However, CD99 expression is an imperfect marker, as some similar tumors can express CD99. The present invention provides methods of diagnosing Ewing's sarcoma comprising detecting in a test sample of cells to be analyzed for Ewing's sarcoma the expression of NKX2.2 or one or more NKX2.2 downstream genes, wherein the downstream genes are up- or down-regulated by NKX2.2 in cells of Ewing's sarcoma; and comparing the expression of NKX2.2 or one or more of the downstream genes in the test sample to the expression of NKX2.2 or one or more of the downstream genes in a control, wherein the control comprises cells where Ewing's sarcoma is absent, and wherein a difference in expression between the test sample and the control indicates cells of Ewing's sarcoma in the sample.
Strengths:
Weaknesses:
Patent Status:
Inventor Bio: Stephen L. Lessnick
http://www.nationwidechildrens.org/news-room-articles/stephen-l-lessnick-md-phd-named-director-of-the-center-for-childhood-cancer-and-blood-diseases-at-nationwide-childrens-hospital?contentid=143200
Executive Summary:
- Invention Type: Diagnostic/Therapeutic
- Patent Status: Issued (Grant date: 2011-05-10)
- Patent Link: https://patents.google.com/patent/US7939253/
- Research Institute: University of Utah Research Foundation
- Disease Focus: Ewing's sarcoma
- Basis of Invention: NKX2.2 gene is an independently reproduced biomarker for Ewing's sarcoma, but is not used in the published inventions to diagnose or treat this cancer
- How it works: Measuring the amount of mRNA transcript of NKX2.2 present in the sample comprises amplifying the transcript of NKX2.2 by PCR and detecting the amplification products and microarray analysis
- Lead Challenge Inventor: Stephen L. Lessnick
- Development Stage: Patient-derived tumor samples
- Novelty: No similar commercial product available
- Clinical Applications: Specific diagnostic tool and potential therapeutic target for Ewing's sarcoma
General Description:
Ewing's sarcoma is an aggressive and highly metastatic malignancy and it arises in and around the bones of the extremities and central skeleton, but may also arise in the soft tissues as “extraosseous Ewing's.” Ewing's sarcoma primarily affects children and young adults, predominantly those of European descent, with the highest rates of development occurring in white male adolescents.
The diagnosis of Ewing's sarcoma is typically based on histologic criteria and associated expression of EWS/FLI. The majority of the translocations code for EWS/FLI. However, a minority of translocations encode fusions that are similar, but not identical to EWS/FLI. Consequently, molecular diagnostics that test for EWS/FLI, such as quantitative PCR, miss approximately 15% of Ewing's sarcoma cases. Immunohistochemistry is a more wide-spread and readily applied technique for diagnosis. The most specific and sensitive immunohistochemical marker for Ewing's sarcoma is CD99 expression. However, CD99 expression is an imperfect marker, as some similar tumors can express CD99. The present invention provides methods of diagnosing Ewing's sarcoma comprising detecting in a test sample of cells to be analyzed for Ewing's sarcoma the expression of NKX2.2 or one or more NKX2.2 downstream genes, wherein the downstream genes are up- or down-regulated by NKX2.2 in cells of Ewing's sarcoma; and comparing the expression of NKX2.2 or one or more of the downstream genes in the test sample to the expression of NKX2.2 or one or more of the downstream genes in a control, wherein the control comprises cells where Ewing's sarcoma is absent, and wherein a difference in expression between the test sample and the control indicates cells of Ewing's sarcoma in the sample.
Strengths:
- The technique may be more versatile that the existing ones
Weaknesses:
- Cost may be an issue
Patent Status:
- Priority date: 2007-05-09
- Filing date: 2007-05-09
- Publication date: 2011-05-10
- Grant date: 2011-05-10
Inventor Bio: Stephen L. Lessnick
http://www.nationwidechildrens.org/news-room-articles/stephen-l-lessnick-md-phd-named-director-of-the-center-for-childhood-cancer-and-blood-diseases-at-nationwide-childrens-hospital?contentid=143200
