{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:57:18Z","timestamp":1770749838062,"version":"3.50.0"},"reference-count":26,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> KRAS is the most mutated proto-oncogene that has been identified in cancer, and treatment of patients with KRAS mutations remains an arduous challenge. Recently, KRAS<jats:sup> G12C<\/jats:sup> mutation has attracted special interest because it is now considered potentially druggable with recently developed covalent small-molecule KRAS<jats:sup> G12C<\/jats:sup> inhibitors. Nevertheless, to date, there have been no large-scale analyses of liquid biopsy that include testing for KRAS<jats:sup> G12C<\/jats:sup>. Here, we performed a comprehensive analysis of KRAS<jats:sup> G12C<\/jats:sup> mutations in multiple cancer types, as detected by circulating tumor DNA. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> We conducted a 5-year retrospective review of KRAS<jats:sup> G12C<\/jats:sup> mutations in patients with cancer who had undergone Guardant360 testing between July 1, 2014, and June 30, 2019; our study included treatment-naive and previously treated patients with metastatic solid tumors. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> KRAS<jats:sup> G12C<\/jats:sup> mutations were identified in 2,985 of 80,911 patients (3.7%), across &gt; 40 tumor types. KRAS<jats:sup> G12C<\/jats:sup> mutations were detected most frequently in patients with nonsquamous non\u2013small-cell lung cancer (NSCLC; 7.5%), NSCLC of all subtypes (6.9%), cancer of unknown primary (4.1%), colorectal cancer (3.5%), squamous NSCLC (2.0%), pulmonary neuroendocrine tumors (1.9%), and pancreatic ductal adenocarcinoma (1.2%) and cholangiocarcinoma (1.2%). KRAS<jats:sup> G12C<\/jats:sup> mutations were predominantly clonal (clonality &gt; 0.9%) in patients with lung adenocarcinoma, non-NSCLC, cancer of unknown primary, NSCLC, and pancreatic ductal adenocarcinoma, and patients with colorectal cancer and breast cancer had bimodal distribution of clonal and subclonal KRAS<jats:sup> G12C<\/jats:sup> mutations. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Our study demonstrates the feasibility of using circulating tumor DNA to identify KRAS<jats:sup> G12C<\/jats:sup> mutations across solid tumors; the highest detection rate was in lung cancer, as previously reported in the literature. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.21.00547","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T19:59:31Z","timestamp":1658433571000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Identification of <i>KRAS<\/i><sup><i>G12C<\/i><\/sup> Mutations in Circulating Tumor DNA in Patients With Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1518-1097","authenticated-orcid":false,"given":"Kyaw Z.","family":"Thein","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"Division of Hematology and Medical Oncology, Oregon Health and Science University\/Knight Cancer Institute, Portland, OR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amadeo B.","family":"Biter","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly C.","family":"Banks","sequence":"additional","affiliation":[{"name":"Guardant Health, Inc., Redwood City, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew W.","family":"Duda","sequence":"additional","affiliation":[{"name":"Guardant Health, Inc., Redwood City, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Saam","sequence":"additional","affiliation":[{"name":"Guardant Health, Inc., Redwood City, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-6170","authenticated-orcid":false,"given":"Jason","family":"Roszik","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-4065","authenticated-orcid":false,"given":"Filip","family":"Janku","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinandos","family":"Skoulidis","sequence":"additional","affiliation":[{"name":"Department of Thoracic-Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-8942","authenticated-orcid":false,"given":"John V.","family":"Heymach","sequence":"additional","affiliation":[{"name":"Department of Thoracic-Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9647-3416","authenticated-orcid":false,"given":"Scott","family":"Kopetz","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 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