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

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.

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Cite

BibTeX RIS

BibTeX

@article{shreenivas2026circulating,
  title = {{Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood}},
  author = {Aditya Shreenivas and Sewanti Limaye and Massimo Cristofanilli and Matt Lechner and Andrew M. Gaya and Tim Crook and Pollyanna Leite and Kefah Mokbel and Dorthe Schaffrin-Nabe and Humaid O. Al-Shamsi and Darshana Patil and Rajan Datar and Razelle Kurzrock},
  journal = {iScience},
  year = {2026},
  month = oct,
  doi = {10.1016/j.isci.2026.117893},
  url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03276-1},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - Circulating tumor DNA in body fluids for molecular characterization of cancers beyond tissue and blood
AU  - Aditya Shreenivas
AU  - Sewanti Limaye
AU  - Massimo Cristofanilli
AU  - Matt Lechner
AU  - Andrew M. Gaya
AU  - Tim Crook
AU  - Pollyanna Leite
AU  - Kefah Mokbel
AU  - Dorthe Schaffrin-Nabe
AU  - Humaid O. Al-Shamsi
AU  - Darshana Patil
AU  - Rajan Datar
AU  - Razelle Kurzrock
PY  - 2026
DA  - 2026/10/14
JO  - iScience
DO  - 10.1016/j.isci.2026.117893
UR  - https://www.cell.com/iscience/fulltext/S2589-0042(26)03276-1
AB  - 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.
SN  - 2589-0042
ER  -

Abstract

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