{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:27Z","timestamp":1790794527632,"version":"4.1.0"},"reference-count":63,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["ZIA BC011793"],"award-info":[{"award-number":["ZIA BC011793"]}]},{"name":"European Research Council","award":["ERC Adg #101019560"],"award-info":[{"award-number":["ERC Adg #101019560"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Small-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis and marked transcriptional heterogeneity that may drive distinct therapeutic vulnerabilities. Clinical translation of molecular subtyping has been limited by restricted access to tumor biopsies, particularly at relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We applied chromatin immunoprecipitation of cell-free nucleosomes carrying active histone modifications followed by sequencing (cfChIP-seq) to 441 plasma samples from individuals with advanced SCLC, other neuroendocrine carcinomas, or non-SCLC cancers, as well as from healthy controls. Plasma cfChIP-seq profiles were integrated with matched tumor transcriptomes from 73 samples, including 41 time-matched pairs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      cfChIP-seq captured the epigenetic and transcriptional landscape of tumor-derived cell-free DNA (cfDNA), including SCLC tissue- and cell-of-origin signatures. A quantitative cfChIP-seq\u2013derived SCLC score tracked radiographic tumor burden and was associated with prognosis. Signals at promoters of lineage-defining transcription factor genes, including\n                      <jats:italic>ASCL1<\/jats:italic>\n                      ,\n                      <jats:italic>NEUROD1<\/jats:italic>\n                      ,\n                      <jats:italic>POU2F3<\/jats:italic>\n                      , and\n                      <jats:italic>ATOH1<\/jats:italic>\n                      , correlated strongly with matched tumor RNA expression and supported noninvasive inference of SCLC transcriptional subtypes directly from plasma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Plasma cfChIP-seq provides a practical liquid biopsy platform for real-time assessment of tumor burden, tumor state, and molecular subtype in SCLC. These findings support further development of cfChIP-seq for precision monitoring and subtype-informed therapeutic stratification in SCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT02484404, NCT02487095, NCT02769962, NCT03554473, NCT03896503, and NCT02146170.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Center for Cancer Research; Intramural Program of the NCI (ZIA BC 011793); European Research Council (ERC) (Adg no. 101019560 \u201ccfChIP\u201d).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci202151","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:01:22Z","timestamp":1790791282000},"source":"Crossref","is-referenced-by-count":0,"title":["Plasma nucleosome profiling reports on 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