{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12"],"submitter":["Ko TK"],"funding":["Agency for Science, Technology and Research","SingHealth Foundation","Duke-NUS Medical School","National Medical Research Council"],"pubmed_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<sup>®</sup> LiquidPlex™ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor <i>KIT</i> mutations (<i>n</i> = 41, 89.1%), while 3 were <i>PDGFRA</i> exon 18 D842V mutants and the rest (<i>n</i> = 2) were wild type for <i>KIT</i> and <i>PDGFRA</i>. In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest (<i>n</i> = 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 <i>KIT</i> (<i>n</i> = 5) or <i>PDGFRA</i> (<i>n</i> = 1) in ctDNA were identified only among 6 of the 10 patients. These <i>KIT</i> 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 <i>KIT</i>-mutant GIST, tumor burden was higher with detectable <i>KIT</i> ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, <i>p</i> = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases (<i>n</i> = 14) or metastatic cases without evidence of disease progression (<i>n</i> = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable <i>PIK3CA</i> 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."],"journal":["Frontiers in oncology"],"pagination":["840843"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8904145"],"repository":["biostudies-literature"],"pubmed_title":["Circulating Tumor DNA Mutations in Progressive Gastrointestinal Stromal Tumors Identify Biomarkers of Treatment Resistance and Uncover Potential Therapeutic Strategies."],"pmcid":["PMC8904145"],"pubmed_authors":["Ko TK","Somasundaram N","Yang VS","Ng CC","Teh BT","Farid M","Lee E","Chan JY"],"additional_accession":[]},"is_claimable":false,"name":"Circulating Tumor DNA Mutations in Progressive Gastrointestinal Stromal Tumors Identify Biomarkers of Treatment Resistance and Uncover Potential Therapeutic Strategies.","description":"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<sup>®</sup> LiquidPlex™ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor <i>KIT</i> mutations (<i>n</i> = 41, 89.1%), while 3 were <i>PDGFRA</i> exon 18 D842V mutants and the rest (<i>n</i> = 2) were wild type for <i>KIT</i> and <i>PDGFRA</i>. In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest (<i>n</i> = 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 <i>KIT</i> (<i>n</i> = 5) or <i>PDGFRA</i> (<i>n</i> = 1) in ctDNA were identified only among 6 of the 10 patients. These <i>KIT</i> 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 <i>KIT</i>-mutant GIST, tumor burden was higher with detectable <i>KIT</i> ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, <i>p</i> = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases (<i>n</i> = 14) or metastatic cases without evidence of disease progression (<i>n</i> = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable <i>PIK3CA</i> 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2025-04-04T14:49:53.604Z","creation":"2025-04-04T14:49:53.604Z"},"accession":"S-EPMC8904145","cross_references":{"pubmed":["35273917"],"doi":["10.3389/fonc.2022.840843"]}}