Genomic <i>EWSR1</i> Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma

Krumbholz, Manuela; Hellberg, Julia; Steif, Benedikt; Bäuerle, Tobias; Gillmann, Clarissa; Fritscher, Torsten; Agaimy, Abbas; Frey, Benjamin; Juengert, Joerg; Wardelmann, Eva; Hartmann, Wolfgang; Juergens, Heribert; Dirksen, Uta; Metzler, Markus

doi:10.1158/1078-0432.ccr-15-3028

Cited by 74 publications

(80 citation statements)

References 36 publications

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“…Detection of circulating tumor cells and circulating tumor DNA (“liquid biopsies”) plays an emerging role as non-invasive diagnostic and disease monitoring tool. Liquid biopsies are now being evaluated for neuroblastoma and Ewing sarcoma [8, 9]. …”

Section: Reviewmentioning

confidence: 99%

Precision medicine in pediatric oncology

et al. 2018

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Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.

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Section: Reviewmentioning

confidence: 99%

Precision medicine in pediatric oncology

et al. 2018

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“…As amplification of the target region is performed with primers binding to separate chromosomal regions and detection of the target amplicon occurs by a probe that is placed on the breakpoint region, these assays offer unprecedented specificity. The feasibility of this approach has also recently been confirmed in Ewing sarcomas . The assays to detect synovial sarcoma t(X;18) ctDNA from cell‐lines showed similar sensitivity and specificity than with myxoid liposarcomas (Fig.…”

Section: Discussionmentioning

confidence: 81%

Genotyping of circulating cell‐free DNA enables noninvasive tumor detection in myxoid liposarcomas

Braig

Becherer

Bickert

et al. 2019

Intl Journal of Cancer

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Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin. About 50% of patients with STS experience relapse and more than 30% will die within 10 years after diagnosis. In this study we investigated circulating free DNA (cfDNA) and tumor‐specific genetic alterations therein (circulating tumor DNA, ctDNA) as diagnostic biomarkers. Plasma concentrations and fragmentation of cfDNA was analyzed with quantitative PCR. Patients with STS (n = 64) had significantly higher plasma concentrations and increased fragmentation of cfDNA when compared to patients in complete remission (n = 19) and healthy controls (n = 41) (p < 0.01 and p < 0.001). Due to overlapping values between patients with STS and controls, the sensitivity and specificity of these assays is limited. Sensitive assays to detect genomic alterations in cfDNA of synovial sarcomas (t(X;18)), myxoid liposarcomas (t(12;16) and TERT C228T promoter mutation) and well‐differentiated/de‐differentiated liposarcomas (MDM2 amplifications) were established. ctDNA was quantified in nine liposarcoma patients during the course of their treatment. Levels of breakpoint t(12;16) and TERT C228T ctDNA correlated with the clinical course and tumor burden in patients with myxoid liposarcomas (n = 4). ctDNA could detect minimal residual disease and tumor recurrence. In contrast, detection of MDM2 amplifications was not sensitive enough to detect tumors in patients with well‐differentiated/de‐differentiated liposarcomas (n = 5). Genotyping of cfDNA for tumor specific genetic alterations is a feasible and promising approach for monitoring tumor activity in patients with myxoid liposarcomas. Detection of ctDNA during follow‐up examinations despite negative standard imaging studies might warrant more sensitive imaging (e.g. PET‐CT) or closer follow‐up intervals to timely localize and treat recurrences.

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“…17–18 This case highlights the potential utility of circulating tumor DNA as a blood based biomarker for ES, particularly in situations where biopsy confers significant morbidity. Our group has recently demonstrated that EWSR1 fusions can be detected via blood droplet digital PCR in 11/11 ES patients, 7 of which were able to be detected at relapse.…”

Section: Discussionmentioning

confidence: 94%

Intracardiac Low-grade Sarcoma Following Treatment for Ewing Sarcoma

Ortiz

Magnan

Slotkin

et al. 2017

Journal of Pediatric Hematology/Oncology

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A 16 year old young man was diagnosed with Ewing sarcoma of the ribcage with pulmonary metastases. Six months after completion of scheduled therapy he was found to have a new intracardiac mass, presumed recurrent Ewing sarcoma. EWSR1 fusion was not detected via droplet digital PCR from blood plasma. After no improvement with salvage chemotherapy, he underwent surgical resection which identified a low-grade spindle cell sarcoma. Despite the near synchronous presentation of two unrelated sarcomas, extensive genomic analyses did not reveal any unifying somatic or germline mutations nor any apparent cancer predisposition. This case also highlights the potential role of utilizing plasma cell-free DNA for diagnosing tumors in locations where biopsy confers high morbidity.

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Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma

Cited by 74 publications

References 36 publications

Precision medicine in pediatric oncology

Precision medicine in pediatric oncology

Genotyping of circulating cell‐free DNA enables noninvasive tumor detection in myxoid liposarcomas

Intracardiac Low-grade Sarcoma Following Treatment for Ewing Sarcoma

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