Evidence map›Paper›PMID 42318389›Full record

ArticleFrontiers in medicine2026

Cancer of unknown primary genomic profiling from cell-free DNA provides insights into CUP biology and vulnerabilities.

Roberta Roncarati, Beatrice Fontana, Ilaria Pace, Giorgio Durante, Nicole Conci, Alessia Soru, Giulia Gallerani, Mattia Riefolo, Irene Salamon, Noemi Laprovitera and 9 more

Abstract read
In one paragraph

Article in Frontiers in medicine, 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

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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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

19 authors.

Roberta Roncarati *Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Beatrice Fontana *Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Ilaria Pace *Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Giorgio DuranteIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Nicole ConciDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Alessia SoruDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Giulia GalleraniDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Mattia RiefoloIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Irene SalamonIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Noemi LaproviteraIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Elisabetta BroseghiniIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Maria NaddeoIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Andrea EspisDipartimento di Ingegneria dell'Energia Elettrica e dell'Informazione "Guglielmo Marconi" (DEI), University of Bologna, Bologna, Italy.
Gabriele SalesDepartment of Biology, University of Padova, Padua, Italy.
Stefano DiciottiDipartimento di Ingegneria dell'Energia Elettrica e dell'Informazione "Guglielmo Marconi" (DEI), University of Bologna, Bologna, Italy.
Antonia D'ErricoDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Karim RihawiIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Andrea ArdizzoniDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Manuela FerracinDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Cancer of unknown primary (CUP) is a metastatic malignancy with no identifiable site of origin, accounting for 2-5% of cancer diagnoses. Its marked heterogeneity and the limited availability of tumor tissue pose major challenges to genomic profiling. Methods: In this retrospective observational study, we applied a 92-gene CUP-specific targeted sequencing panel to liquid biopsy samples from 39 CUP patients, analyzing circulating cell-free DNA (ccfDNA) together with paired germline DNA (gDNA), when available. Somatic, germline, and CHIP-related variants were classified using predefined variant allele frequency (VAF) thresholds and paired ccfDNA/gDNA comparison. Results: We identified somatic mutations in 78 of 92 genes and 44 clinically relevant variants (Tier I-III), most frequently affecting Discussion: Overall, these findings support liquid biopsy as a valuable approach for molecular profiling of CUP and highlight the critical importance of paired ccfDNA/gDNA analysis, including CHIP assessment, to accurately distinguish somatic, germline, and hematopoiesis-related variants.

Indexed as

cancer geneticscancer of unknown primaryCHIPliquid biopsyprecision oncologytarget therapy

Identifiers

PMID42318389
PMCPMC13271982

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