Investigators: Brian D. Crompton, MD, PhD; Suzanne George, MD
Institution: Dana-Farber Cancer Institute, Boston Children’s Hospital
Clinical Challenge
- Uterine leiomyosarcoma are rare, highly aggressive malignancies that can mimic benign fibroids.
- Because no blood- or imaging-based biomarker reliably distinguishes these cancers pre-operatively, many uterine sarcomas are discovered only after hysterectomy or at metastatic presentation.
- This diagnostic gap delays curative intervention and exposes women to life-altering surgeries and risk for what may be undetected malignancies.
Innovation
- Liquid biopsy using circulating tumor DNA (ctDNA) enables non-invasive, tumor-specific detection of malignancy.
- Crompton and George previously demonstrated ctDNA can identify and track leiomyosarcoma, correlating with tumor burden and treatment response (Clin Cancer Res 2022; Cancers 2022; Hematol Oncol Clin N Am 2025).
- Advanced fragmentomic and methylation profiling technologies now allow for more sensitive assays that may differentiate fibroids from sarcoma.
Proposed DFF-Funded Approach
- Develop and validate ctDNA-based assays for early detection of LMS.
- Analyze plasma/tumor samples from LMS patients and leiomyoma controls.
- Apply methylation whole-genome sequencing to identify tumor-specific ctDNA patterns.
Impact
- Establish the first non-invasive liquid biopsy-based platform for early detection of uterine sarcomas.
- Reduce delayed or missed diagnoses in women with life-threatening malignancies.
- Establish a foundation for a “sarcoma signature” blood test.
Join with DFF in Partnering for Early Detection and Discovery
- Supporting ctDNA assay development and validation for early detection of uterine LMS.
- Optimizing assay for detecting minimal residual disease and early recurrence.
- Accelerating clinical translation of ctDNA testing as a practical diagnostic and monitoring tool for women at risk of uterine sarcomas.
