In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 24, No. 2_Supplement ( 2018-01-15), p. A08-A08
Abstract:
The CircSarc study aims to provide new insights into the clinical utility of liquid biopsies in sarcomas. Today, mutational profiles of solid tumors are obtained from tissue biopsies or surgical specimens. Recent advances in technology now allows to use blood plasma as a “liquid biopsy,” examining circulating tumor DNA (ctDNA) shed by the tumor cells into peripheral blood. ctDNA in plasma carries tumor-specific alterations that can be used to monitor minimal residual disease, response to therapy, tumor burden and evolution throughout the course of the disease. In CircSarc, we have enrolled 30 high-grade soft-tissue sarcoma patients, with localized disease, who are being followed throughout the course of their disease. Plasma from each patient is collected longitudinally: before and after surgery, at each routine control, and before and after each treatment cycle. Patients' tumor and germline DNA were exome sequenced to identify tumor-specific mutations, and ctDNA is being sequenced using a comprehensive 900 cancer gene panel. The level of ctDNA in plasma, represented by the tumor-specific biomarkers, is then monitored throughout the course of the treatment, and acts as an indicator of tumor burden. In addition, we are analyzing plasma samples from 70 gastrointestinal stroma tumor (GIST) samples using targeted resequencing with Anchored Multiplex PCR (ArcherDX). The levels of KIT and PDGFRA mutations in ctDNA are being correlated with clinical and pathologic features. The established targeted resequencing protocols for ctDNA provide different levels of complexity and sensitivity. In the first screening, we have successfully detected somatic mutations in plasma at time of surgery in 70% of the samples analyzed. Mutations present in the tumor at an allele frequency larger than 20% can be robustly identified in plasma. In addition, analysis of plasma samples identified novel mutations not detected in the primary tumor, possibly reflecting intratumor heterogeneity. Similarly, analysis of plasma from GIST patients has identified ctDNA in over 50% of the cases analyzed. In selected cases, ctDNA sequencing has revealed tumor heterogeneity, which has been confirmed by spatial biopsies of the resected tumor. Our work provides new insights into the clinical significance of ctDNA in sarcomas. By repeated sampling of liquid biopsies, somatic mutations identified in ctDNA can be used as unique noninvasive tumor-specific biomarkers for monitoring tumor burden and disease evolution throughout the course of the disease. Citation Format: Heidi M. Namløs, Seyed Hossein Moosavi, Susanne Lorenz, Bodil Bjerkehagen, Olga Zaikova, Synnøve Granlien, Stine Næss, Eva Stratford, Else Munthe, Lars B. Aasheim, Sigve Nakken, Eivind Hovig, Nina L. Jebsen, Kirsten Sundby Hall, Skyler Mishkin, Brian Kudlow, Ola Myklebost, Kjetil Boye, Leonardo A. Meza-Zepeda. Disease monitoring by liquid biopsies in sarcomas [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A08.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1557-3265.SARCOMAS17-A08
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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