Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood

Liquid biopsy using circulating tumor DNA (ctDNA) is increasingly used for cancer profiling and monitoring, but blood-based analysis may not capture tumor heterogeneity across anatomical compartments. We evaluated cell-free DNA from cerebrospinal ( n = 7), pleural ( n = 11), pericardial ( n = 1), and ascitic ( n = 26) fluids from 45 patients with advanced cancer, comparing molecular findings with matched tissue, blood, and cytology where available. Oncogenic alterations were detected in 87% of body fluid samples, with a median variant allele frequency of 3.15%. TP53 (49%), EGFR (18%), and KRAS (18%) were the most frequently altered genes, and ESCAT tier IA alterations occurred in 31.1% of patients. In six patients (13.3%), potentially targetable alterations were detected in body fluids but not in blood and/or tissue. Among five cytology-negative samples, four were ctDNA positive. These findings support body fluid ctDNA profiling as a complementary approach to tissue, plasma, and cytology, thereby warranting prospective validation.

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Publication Details

Journal
iScience
Published
2026-10-14
DOI
https://doi.org/10.1016/j.isci.2026.117893
Primary Topic
Cancer Genomics and Diagnostics
Type
article
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article

Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood

Humaid Obaid Al-Shamsi, Rajan Datar, Andrew M. Gaya, Razelle Kurzrock et al.
iScience
Cancer Genomics and Diagnostics
article

Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood

Humaid Obaid Al-Shamsi, Rajan Datar, Andrew M. Gaya, Razelle Kurzrock, Aditya Varnam Shreenivas, Sewanti Atul Limaye, Darshana Patil, Matt Lechner, Tim J. Crook, Massimo Cristofanilli, Pollyanna Leite, Dorthe Schaffrin-Nabe, Kefah Mokbel
article en

Abstract

Liquid biopsy using circulating tumor DNA (ctDNA) is increasingly used for cancer profiling and monitoring, but blood-based analysis may not capture tumor heterogeneity across anatomical compartments. We evaluated cell-free DNA from cerebrospinal ( n = 7), pleural ( n = 11), pericardial ( n = 1), and ascitic ( n = 26) fluids from 45 patients with advanced cancer, comparing molecular findings with matched tissue, blood, and cytology where available. Oncogenic alterations were detected in 87% of body fluid samples, with a median variant allele frequency of 3.15%. TP53 (49%), EGFR (18%), and KRAS (18%) were the most frequently altered genes, and ESCAT tier IA alterations occurred in 31.1% of patients. In six patients (13.3%), potentially targetable alterations were detected in body fluids but not in blood and/or tissue. Among five cytology-negative samples, four were ctDNA positive. These findings support body fluid ctDNA profiling as a complementary approach to tissue, plasma, and cytology, thereby warranting prospective validation.

iScienceVol. 29(11)
City Of Hope National Medical Center (US), Froedtert Hospital (US), NewYork–Presbyterian Hospital (US), Harvard University (US), Imperial College Healthcare NHS Trust (GB), Medical College of Wisconsin (US), Cornell University (US), Sir H.N. Reliance Foundation Hospital and Research Centre (IN), Dana-Farber Cancer Institute (US), The Princess Grace Hospital (GB), Datar Cancer Genetics (India) (IN), Praxis für Hämatologie und Onkologie (DE), Bupa Cromwell Hospital (GB), WIN Consortium, Medical College of Wisconsin Cancer Center, University College London (GB), University of Nebraska Medical Center (US), Ras al-Khaimah Medical and Health Sciences University (AE)
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Openalex Percentile: Top 18%
Cancer Genomics and Diagnostics
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