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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
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Programmable Self-Priming Lanthanide-DNA Probes Enabling Multiplexed Single-Cell Quantification of Glioma Splice

Nan Zhang1, Zhiyong Yan2, Fangxue Gu3

  • 1Beijing Engineering Research Center of Mixed Reality and Advanced Display, School of Optics and Photonics, Beijing Institute of Technology, Beijing 100081, China.

Analytical Chemistry
|June 10, 2026
PubMed
Summary

A new DNA probe strategy enables precise, single-cell measurement of multiple MDM2 splice variants in glioma cells. This breakthrough aids in understanding tumor heterogeneity and discovering new cancer biomarkers.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Alternative splicing creates diverse mRNA isoforms, contributing to protein diversity and tumor heterogeneity.
  • Accurate, multiplexed quantification of splice variants at the single-cell level is challenging.
  • Understanding splice variant expression is crucial for cancer research and diagnostics.

Purpose of the Study:

  • To develop a novel method for sensitive, multiplexed single-cell quantification of MDM2 splice variants.
  • To apply this method to glioma-related cell models for analyzing tumor heterogeneity.
  • To overcome limitations of existing bulk and sequencing-based approaches.

Main Methods:

  • Programmable self-priming lanthanide-labeled DNA probes (PSPLn) were designed with tunable adenine sequences.
  • Click chemistry was used to conjugate distinct lanthanide-DOTA complexes for junction-specific recognition.
  • Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was employed for high-throughput, single-cell analysis.

Main Results:

  • The PSPLn strategy achieved sensitive and multiplexed quantification of MDM2 splice variants in single cells.
  • Variant-dependent expression profiles and intervariant correlation patterns were identified in glioblastoma and oligodendrocytic cell lines.
  • The method demonstrated high-throughput, single-cell readout capabilities.

Conclusions:

  • The PSPLn-LA-ICP-MS platform offers a versatile tool for splice variant analysis at single-cell resolution.
  • This approach overcomes limitations of traditional methods, enabling detailed study of tumor heterogeneity.
  • It holds potential for splice biomarker discovery and advancing precision diagnostics in oncology.