Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas

Bone & Joint Research

article

Kim M. Tsoi¹  Nalan Gokgoz²  Paige Darville-O'Quinn²  Patrick Prochazka²  Ainaz Malekoltojari²  Anthony M. Griffin¹  Peter C. Ferguson¹  Jay S. Wunder¹  Irene L. Andrulis² 

[1] University of Toronto Musculoskeletal Oncology Unit, Sinai Health System;Lunenfeld-Tanenbaum Research Institute, Sinai Health System

关键词: Sarcoma;    Cell-free DNA;    Circulating tumour DNA;    soft-tissue sarcomas;    DNAs;    Sarcomas;    blood;    biomarkers;    carcinomas;    polymerase chain reaction;    cancers;    chondrosarcoma;    quantitative PCR;   

DOI  :  10.1302/2046-3758.109.BJR-2021-0014.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsCell-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.MethodsMatched 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).Results6 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.ConclusionThis 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.

【 授权许可】

CC BY-NC