Evidence map›Paper›PMID 42635246›Full record

ArticleBioinformatics (Oxford, England)2026

Liquid biopsies reveal dual compartments of cancer risk from tumor and host-derived mutations.

Federica Malighetti, Ivan Civettini, Andrea Aroldi, Alberto Maria Villa, Matteo Villa, Luca Sala, Nicoletta Cordani, Massimiliano Cadamuro, Diego Cortinovis, Rocco Piazza and 2 more

Abstract read
In one paragraph

Article in Bioinformatics (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Federica MalighettiDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Ivan CivettiniDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Andrea AroldiDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Alberto Maria VillaDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Matteo VillaDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Luca SalaFondazione IRCCS San Gerardo dei Tintori di Monza, Monza, Italy.ORCID 0000-0003-4568-5739
Nicoletta CordaniDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Massimiliano CadamuroDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Diego CortinovisDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Rocco PiazzaDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Luca MologniDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
Daniele RamazzottiDepartment of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.ORCID 0000-0002-6087-2666

Funding

AIRC fellowship for ItalyItalian Foundation for Cancer Research (AIRC) under MFAG 24828Italian Foundation for Cancer Research (AIRC) under MFAG 31886Italian Foundation for Cancer Research (AIRC) under MFAG IG 2020Oxiamo ONLUS
6 · The paper itself

Abstract

motivationCirculating 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-resolved analysis of over 9000 patients with CHIP data and 1500 patients with ctDNA data across solid tumors profiled at Memorial Sloan Kettering Cancer Center.

resultsOur 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. AVAILABILITY: All genomic and clinical data used in this study are available through cBioPortal. Summarized outputs and processed results tables are provided in Supplementary Data.

Indexed as

Circulating Tumor DNAMutationNeoplasmsBiomarkers, TumorClonal HematopoiesisHumansLiquid BiopsyPrognosisBiomarkers, TumorCirculating Tumor DNA

Identifiers

PMID42635246
PMCPMC13501295

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