Journal
BONE & JOINT RESEARCH
Volume 10, Issue 9, Pages 602-610Publisher
BRITISH EDITORIAL SOC BONE & JOINT SURGERY
DOI: 10.1302/2046-3758.109.BJR-2021-0014.R1
Keywords
Sarcoma; Cell-free DNA; Circulating tumour DNA
Categories
Funding
- Division of Orthopaedic Surgery, Sinai Health System
Ask authors/readers for more resources
This study investigated the prognostic significance of cfDNA and ctDNA in bone and soft-tissue sarcomas, demonstrating their potential as biomarkers despite the lack of recurrent genomic alterations. Patients with lower cfDNA levels showed improved disease-free survival rates. Digital droplet PCR was able to detect tumor-specific alterations in the circulation of sarcoma patients.
Aims Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Methods Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR). Results Cell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for <= 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases. Conclusion This work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and soft-tissue sarcomas, despite the lack of recurrent genomic alterations. A larger study is required to validate these findings.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available