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Monday, 01 October 2018

An optical biosensor methodology to detect DNA-methylation marks involved in cancer

The work, led by the ICN2 Nanobiosensors and Bioanalytical Applications Group, provides an approach based on poly-purine reverse-Hoogsteen (PPRH) probes. It turned out to be a more reliable and fast analysis than conventional techniques. Prof. Manel Esteller, a global authority in the study of epigenetics of cancer, is among the authors of the article published in Biosensors and Bioelectronics.

Tumor cells present different patterns of DNA methylation in comparison to normal cells. These patterns are unique for each cancer type. In fact, DNA methylation profiling has proven to give a consistent diagnosis of the primary tumor even in cases where the primary site of the cancer is unknown. Quantitative analysis of these epigenetic marks can be useful in the early diagnosis and monitoring of tumor progression and response to treatment.

A work recently published in Biosensors and Bioelectronics presents an optical biosensor methodology based on poly-purine reverse-Hoogsteen (PPRH) probes capable of capturing in a straightforward manner specific double-stranded DNA (ds-DNA) fragments by triple helix formation. The work was led by the ICN2 Nanobiosensors and Bioanalytical Applications Group, with Dr César S. Huertas as its first author and Group Leader Prof. Laura Lechuga as the last one. The work was possible through collaboration within the Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) including authors from the Institute for Advanced Chemistry of Catalonia (IQAC) and the Cancer Epigenetics and Biology Program of the Bellvitge Biomedical Research Institute. Prof. Manel Esteller, a global authority in the study of epigenetics of cancer, co-authored this work that might have an impact on cancer diagnostics.

In order to develop individualized therapies and competent follow-up treatments the development of efficient devices combining an accurate quantification with high sensitivity and specificity, minimizing both the resources and the time employed, is needed. The approach suggested in the present article skips the laborious steps prior to other detection procedures by analysing the methylation status directly from ds-DNA fragments. It uses PPRH oligonucleotides capable of capturing specific ds-DNA fragments forming a three-stranded (triplex) conformation.

The biosensor methodology was designed to detect DNA-methylation marks in a specific fragment of PAX-5 gene, which plays an important role in cell differentiation and embryologic development and shows aberrant hypermethylation in tumor cell lines as well as in primary tumors of breast and lung cancer. This biosensor strategy provides a more reliable and fast analysis than conventional techniques. The results also place the new methodology in the front line for the development of biosensor devices that may require the direct capture of ds-DNA fragments, such as circulating cell-free DNA, and the presence of bacteria or viruses in the host organism.

Article reference:
César S. Huertas, Anna Aviñó, Cristina Kurachi, Albert Piqué, Juan Sandoval, Ramón Eritja, Manel Esteller, Laura M. Lechuga. Label-free DNA-methylation detection by direct ds-DNA fragment screening using poly-purine hairpins. Biosensors and Bioelectronics, Volume 120, 30 November 2018, Pages 47-54. https://doi.org/10.1016/j.bios.2018.08.027