A Novel Method for Detecting DNA Defects Toward the Early Diagnosis of Cancer and Other Diseases

As our primary genetic material, DNA fundamentally governs how the human body functions. However, “single-letter” alterations—where just one nucleotide is substituted—can occur. This phenomenon is known as a single-nucleotide polymorphism (SNP) or, in a clinical context, a single-nucleotide variant (SNV). Despite being exceptionally subtle, these variations can contribute to the onset of severe conditions such as cancer or Alzheimer's disease.

Locating such defects is a formidable challenge, akin to spotting a single typographical error in an entire library. Nevertheless, identifying them is crucial, as doing so could pave the way for early detection and prevention strategies.

To tackle this, researchers at HUN-REN Wigner turned to Raman spectroscopy—an analytical technique that uses light to identify molecules. Every molecule possesses a unique "vibrational fingerprint" by which it can be identified.

Until now, implementing this method in biological samples has proved challenging because the signals are weak and frequently overlap. The researchers overcame this hurdle through an ingenious approach: they attached a specific chemical tag—an alkyne group—to the DNA. This produced a strong, highly distinct signal that does not interfere with the natural function of the DNA, yet enables individual nucleotides to be successfully differentiated.

Experiments demonstrated that Raman spectroscopy is capable of tracking not only the hybridisation of DNA strands, but also of identifying the specific nucleotide at a given position. The method was validated against a well-known, cancer-related genetic defect: the BRAF V600E mutation, which is commonly associated with melanoma, among other malignancies. The reproducible measurements successfully and unambiguously distinguished healthy DNA from the mutation-bearing variant.

At present, the technique requires a relatively large sample volume, which limits its immediate clinical application. However, the researchers have already outlined several avenues for development. These include signal enhancement (such as surface-enhanced Raman scattering, or SERS), DNA amplification, and multiplexing—using multiple tags simultaneously to screen for several mutations at once.

In the long term, this novel approach could significantly advance the early detection of cancer, enable screening for disease susceptibility, and foster the development of personalised therapies.

The study was carried out by Miklós Veres, Román Holomb, László Himics, and Tamás Váczi from the Institute for Solid State Physics and Optics at the HUN-REN Wigner Research Centre for Physics, in collaboration with researchers from the University of Birmingham, including the groups of Professors James H.R. Tucker and Ferenc Mueller. The research was conducted under the auspices of the European Innovation Council's NEURAM (ID: 712821) FET-Open project.