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. 2019 Apr 23;9:6413. doi: 10.1038/s41598-019-42855-x

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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The resonance of the methylated DNA in blood cancer cell lines and the quantification of DNA methylation degree. (a) The expected resonance peaks of methylated DNA in the THz spectrum. The THz resonance peaks stem from multiple absorption curves in the same frequency location. The intensity of the THz resonance peak represents the amount of the methyl-DNA bonds in cancer DNA. (b) Baseline correction to clarify the resonance peak in five cancer types (in the clockwise direction, T-cell lymphoma, B-cell lymphoma, Burkitt lymphoma, T-ALL, and AML). The measured data were fitted well with the superposition of two Gaussian functions. One of them is the baseline (emerald area) and represents the background materials (e.g., ice, the structure of DNA), and another function is the projected methyl-DNA bond (red line). According to the results, the projected methylation bond in the blood cancer samples shows the resonance at approximately 1.7 THz. (c) The resonance peaks of methylated DNA and baseline correction to clarify the peaks in different blood cancer cell lines. In the clockwise direction, the cancers are T-cell lymphoma (SU-DHL1), B-cell lymphoma (SU-DHL9, OCI-LY1), Burkitt lymphoma (Raji), T-ALL (CCRF-CEM, Jurkat), and AML (HL-60). Each datum was obtained by the average of three independent waveforms taking a mean value of three measurements at a point. The centre of the peaks is approximately 1.7 THz, and the average FWHM is 0.5 THz. The amplitudes of the peaks range from 10 to 20 cm⁻¹, depending on the type of cancer cell line. (d) Verification of the DNA methylation degree measured by THz-TDS (red bar) by comparing the results with those obtained from the global DNA methylation quantification using the ELISA method (blue bar). The ELISA data were obtained by averaging values from six different measurements. Error bars indicate the standard deviation (THz-TDS < 0.075, and ELISA < 0.091). The THz results mostly agree with the ELISA method, which implies that the global DNA methylation degree could be measured directly using the THz-TDS quantification technique.