التفاصيل البيبلوغرافية
| العنوان: |
Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA. |
| المؤلفون: |
Hayashi, Masanori, Chu, David, Meyer, Christian F., Llosa, Nicolas J., McCarty, Gregory, Morris, Carol D., Levin, Adam S., Wolinsky, Jean‐Paul, Albert, Catherine M., Steppan, Diana A., Park, Ben Ho, Loeb, David M., Wolinsky, Jean-Paul |
| المصدر: |
Cancer (0008543X); Oct2016, Vol. 122 Issue 19, p3015-3023, 10p |
| مصطلحات موضوعية: |
SARCOMA, METASTASIS, POLYMERASE chain reaction, XENOGRAFTS, CELL lines, ANIMAL experimentation, ANIMALS, BONE tumors, CANCER relapse, CARRIER proteins, CHROMOSOME abnormalities, DNA, GENES, MICE, OSTEOSARCOMA, PROGNOSIS, PROTEINS, RESEARCH funding, TUMOR classification, CANCER cell culture, DIAGNOSIS |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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