{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:25:50Z","timestamp":1787570750265,"version":"build-2736575974"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Foundation for Cancer Research (AIRC) under MFAG","award":["31886"],"award-info":[{"award-number":["31886"]}]},{"name":"Italian Foundation for Cancer Research (AIRC) under MFAG","award":["IG 2020"],"award-info":[{"award-number":["IG 2020"]}]},{"name":"Italian Foundation for Cancer Research (AIRC) under MFAG","award":["24828"],"award-info":[{"award-number":["24828"]}]},{"name":"AIRC fellowship for Italy"},{"name":"Oxiamo ONLUS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Circulating tumor DNA (ctDNA) and clonal hematopoiesis of indeterminate potential (CHIP) are two biologically distinct sources of somatic mutations detectable in blood. While ctDNA captures tumor-intrinsic alterations, CHIP arises from age-related hematopoietic clones and is often considered background noise. Here, we conduct a large-scale, tumor-type\u2013resolved analysis of over 9000 patients with CHIP data and 1500 patients with ctDNA data across solid tumors profiled at Memorial Sloan Kettering Cancer Center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results reveal that CHIP and ctDNA mutations exhibit non-overlapping, clinically meaningful signals. CHIP mutations, particularly in DNA damage response and epigenetic regulators (e.g. PPM1D, CHEK2, ATM, TP53, ASXL1), are associated with worse overall survival, increased metastatic potential, and site-specific dissemination. ctDNA mutations in canonical oncogenic drivers (e.g. TP53, EGFR, KRAS, STK11) reflect tumor aggressiveness and correlate with poor prognosis and metastasis across multiple cancer types. Joint modeling in lung adenocarcinoma confirms the independent prognostic contributions of both compartments. Additionally, longitudinal clonal analysis links specific CHIP mutations to the emergence of hematologic malignancies under therapeutic pressure. These findings support a dual-compartment model of liquid biopsy, in which tumor- and host-derived mutations jointly inform on cancer risk, progression, and metastatic behavior. Integrating both compartments may enhance the clinical utility of blood-based biomarkers in oncology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability<\/jats:title>\n                    <jats:p>All genomic and clinical data used in this study are available through cBioPortal. Summarized outputs and processed results tables are provided in Supplementary Data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag491","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:49:44Z","timestamp":1782992984000},"source":"Crossref","is-referenced-by-count":0,"title":["Liquid biopsies reveal dual compartments of cancer risk from tumor and host-derived mutations"],"prefix":"10.1093","volume":"42","author":[{"given":"Federica","family":"Malighetti","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Civettini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Experimental Immunology Unit, IRCCS San Raffaele Scientific Institute , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Aroldi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Maria","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4568-5739","authenticated-orcid":false,"given":"Luca","family":"Sala","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Cordani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Cadamuro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Cortinovis","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mologni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-2666","authenticated-orcid":false,"given":"Daniele","family":"Ramazzotti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milano,","place":["Italy"]},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026082407034899700_btag491-B1","doi-asserted-by":"publisher","first-page":"e2300132","DOI":"10.1200\/PO.23.00132","article-title":"Clonal hematopoiesis: updates and implications at the solid tumor-immune interface","volume":"7","author":"Buttigieg","year":"2023","journal-title":"JCO Precis 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