scIRES-seq reveals multimodal molecular heterogeneity in CTCs from small cell cervical cancer
- 1Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Abstract
Circulating tumor cells (CTCs) can provide a window into cellular and molecular mechanisms of cancer dissemination. However, the rarity and heterogeneity of CTCs complicate reliable identification and molecular characterization. Here, we introduce scIRES-seq, a framework linking immunophenotype, genetic variation, epigenomic profiles and gene expression within individual cells. In this proof-of-concept study, we coupled scIRES-seq to real-time imaging spectral flow cytometry and applied it to CTCs from a patient with metastatic cervical small cell neuroendocrine carcinoma. Tumor-matched copy-number alterations and targeted somatic variants established CTC identity, supported by DNA methylation profiles concordant with metastatic tissue and transcriptional features consistent with neuroendocrine differentiation. Genetic and DNA methylation analyses identified two largely concordant CTC subpopulations that were not clearly distinguished by their transcriptomes, highlighting the complementary information gained through single-cell multi-omics profiling. These findings demonstrate the feasibility of integrated CTC identification and characterization and provide a framework for investigating relationships between genetic diversity and molecular states in rare, heterogeneous cell populations.
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BibTeX
@misc{kubitz2026sciresseq,
title = {{scIRES-seq reveals multimodal molecular heterogeneity in CTCs from small cell cervical cancer}},
author = {L. Kubitz and K. Bauer and D. Ordonez-Rueda and M. Schönung and V. Maurer and P. Lajer and S. J. Clark and D. Hübschmann and M.-V. Teleanu and W.-K. Hofmann and S. Schmitt and J.-P. Mallm and S. Fröhling and T. Boch and D. B. Lipka and M. Hartmann},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757279},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757279v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - scIRES-seq reveals multimodal molecular heterogeneity in CTCs from small cell cervical cancer
AU - L. Kubitz
AU - K. Bauer
AU - D. Ordonez-Rueda
AU - M. Schönung
AU - V. Maurer
AU - P. Lajer
AU - S. J. Clark
AU - D. Hübschmann
AU - M.-V. Teleanu
AU - W.-K. Hofmann
AU - S. Schmitt
AU - J.-P. Mallm
AU - S. Fröhling
AU - T. Boch
AU - D. B. Lipka
AU - M. Hartmann
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757279
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757279v1
AB - Circulating tumor cells (CTCs) can provide a window into cellular and molecular mechanisms of cancer dissemination. However, the rarity and heterogeneity of CTCs complicate reliable identification and molecular characterization. Here, we introduce scIRES-seq, a framework linking immunophenotype, genetic variation, epigenomic profiles and gene expression within individual cells. In this proof-of-concept study, we coupled scIRES-seq to real-time imaging spectral flow cytometry and applied it to CTCs from a patient with metastatic cervical small cell neuroendocrine carcinoma. Tumor-matched copy-number alterations and targeted somatic variants established CTC identity, supported by DNA methylation profiles concordant with metastatic tissue and transcriptional features consistent with neuroendocrine differentiation. Genetic and DNA methylation analyses identified two largely concordant CTC subpopulations that were not clearly distinguished by their transcriptomes, highlighting the complementary information gained through single-cell multi-omics profiling. These findings demonstrate the feasibility of integrated CTC identification and characterization and provide a framework for investigating relationships between genetic diversity and molecular states in rare, heterogeneous cell populations.
ER -