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Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA
- Source :
- Cancer. 122:3015-3023
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- Background Even though virtually all patients with Ewing sarcoma achieve a radiographic complete response, up to 30% of patients who present with localized disease and up to 90% of those who present with metastases experience a metastatic disease recurrence, highlighting the inability to identify patients with residual disease at the end of therapy. Up to 95% of Ewing sarcomas carry a driving EWS-ETS translocation that has an intronic breakpoint that is specific to each tumor, and the authors developed a system to quantitatively detect the specific breakpoint DNA fragment in patient plasma. Methods The authors used a long-range multiplex polymerase chain reaction (PCR) technique to identify tumor-specific EWS-ETS breakpoints in Ewing sarcoma cell lines, patient-derived xenografts, and patient tumors, and this sequence was used to design tumor-specific primer sets to detect plasma tumor DNA (ptDNA) by droplet digital PCR in xenograft-bearing mice and patients. Results Tumor-specific breakpoint DNA fragments were detected in the plasma of xenograft-bearing mice, and the signal correlated with tumor burden during primary tumor growth, after surgical resection, and at the time of metastatic disease recurrence. Furthermore, the authors were able to detect the specific breakpoint in plasma DNA obtained from 3 patients with Ewing sarcoma and in 2 patients the authors were able to detect ptDNA when there was radiographically undetectable disease present. Conclusions The use of droplet digital PCR to detect tumor-specific EWS-ETS fusion gene breakpoint ptDNA fragments can be developed into a highly personalized biomarker of disease recurrence that can be optimized in animal studies for ultimate use in patients. Cancer 2016;122:3015-3023. © 2016 American Cancer Society.
- Subjects :
- 0301 basic medicine
Cancer Research
Pathology
medicine.medical_specialty
business.industry
Breakpoint
Cancer
medicine.disease
Primary tumor
Metastasis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
030220 oncology & carcinogenesis
Multiplex polymerase chain reaction
medicine
Cancer research
Biomarker (medicine)
Digital polymerase chain reaction
Sarcoma
business
Subjects
Details
- ISSN :
- 0008543X
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Cancer
- Accession number :
- edsair.doi...........cdcc0ef495cdf36f70e66780b85d4025