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Circulating Tumor DNA Mutations in Progressive Gastrointestinal Stromal Tumors Identify Biomarkers of Treatment Resistance and Uncover Potential Therapeutic Strategies.
- Source :
-
Frontiers in oncology [Front Oncol] 2022 Feb 22; Vol. 12, pp. 840843. Date of Electronic Publication: 2022 Feb 22 (Print Publication: 2022). - Publication Year :
- 2022
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Abstract
- Liquid biopsy circulating tumor DNA (ctDNA)-based approaches may represent a non-invasive means for molecular interrogation of gastrointestinal stromal tumors (GISTs). We deployed a customized 29-gene Archer <superscript>®</superscript> LiquidPlexâ„¢ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor KIT mutations ( n = 41, 89.1%), while 3 were PDGFRA exon 18 D842V mutants and the rest ( n = 2) were wild type for KIT and PDGFRA . In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest ( n = 32) were metastatic. Among ten patients, including 7 on tyrosine kinase inhibitors, with evidence of disease progression at study inclusion, mutations in ctDNA were detected in 7 cases (70%). Known somatic mutations in KIT ( n = 5) or PDGFRA ( n = 1) in ctDNA were identified only among 6 of the 10 patients. These KIT mutants included duplication, indels, and single-nucleotide variants. The median mutant AF in ctDNA was 11.0% (range, 0.38%-45.0%). In patients with metastatic progressive KIT -mutant GIST, tumor burden was higher with detectable KIT ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, p = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases ( n = 14) or metastatic cases without evidence of disease progression ( n = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable PIK3CA exon 9 c.1633G>A mutation, were detected. ctDNA mutations were not detectable when patients responded to a switch in TKI therapy. In conclusion, detection of GIST-related mutations in ctDNA using a customized targeted NGS panel represents an attractive non-invasive means to obtain clinically tractable information at the time of disease progression.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Ko, Lee, Ng, Yang, Farid, Teh, Chan and Somasundaram.)
Details
- Language :
- English
- ISSN :
- 2234-943X
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in oncology
- Publication Type :
- Academic Journal
- Accession number :
- 35273917
- Full Text :
- https://doi.org/10.3389/fonc.2022.840843