SERS-Based Evaluation of the DNA Methylation Pattern Associated With Progression in Clonal Leukemogenesis of Down Syndrome.

Vlad Moisoiu,Nicolae Leopold,Delia Dima,Andrei Stefancu,Ancuta Jurj,Adrian B Tigu,Ciprian Tomuleasa,Gheorghe Popa,Sabina Iluta,Sorin Man,Anca Colita,Smaranda Arghirescu,Alina-Andreea Zimta,Valentina Sas,Stefania D Iancu,Patric Teodorescu,Sergiu Pasca,Cristina Blag,Cristina Turcas

doi:10.3389/fbioe.2021.703268

Abstract

Here we show that surface-enhanced Raman scattering (SERS) analysis captures the relative hypomethylation of DNA from patients with acute leukemia associated with Down syndrome (AL-DS) compared with patients diagnosed with transient leukemia associated with Down syndrome (TL-DS), an information inferred from the area under the SERS band at 1005 cm–1 attributed to 5-methycytosine. The receiver operating characteristic (ROC) analysis of the area under the SERS band at 1005 cm–1 yielded an area under the curve (AUC) of 0.77 in differentiating between the AL-DS and TL-DS groups. In addition, we showed that DNA from patients with non-DS myeloproliferative neoplasm (non-DS-MPN) is hypomethylated compared to non-DS-AL, the area under the SERS band at 1005 cm–1 yielding an AUC of 0.78 in separating between non-DS-MPN and non-DS-AL. Overall, in this study, the area of the 1005 cm–1 DNA SERS marker band shows a stepwise decrease in DNA global methylation as cells progress from a pre-leukemia to a full-blown acute leukemia, highlighting thus the potential of SERS as an emerging method of analyzing the methylation landscape of DNA in the context of leukemia genesis and progression.

Highlights

DNA methylation is a key factor contributing to the audacity with which cancer cell resist to any form of treatment (Galle et al, 2020)
We focused in this study on patients with Down syndrome (DS) diagnosed with acute leukemia [termed acute leukemia associated with DS (AL-DS)] (Xavier et al, 2009)
The Surface-enhanced Raman scattering (SERS) spectra are dominated by the SERS band at 1005 cm−1 attributed to the rocking vibration of 5-methylcytosine (Moisoiu et al, 2019; Sanchez-Cortés and Garcia-Ramos, 1992), the SERS band at 730 cm−1 tentatively assigned to adenine (Garcia-Rico et al, 2018), the SERS band at 680 cm−1 tentatively assigned to guanine (Garcia-Rico et al, 2018), and the bands at 880 and 920 cm−1 attributed to the DNA backbone (Duguid et al, 1993)

Summary

Introduction

DNA methylation (along with other epigenetic modifications) is a key factor contributing to the audacity with which cancer cell resist to any form of treatment (Galle et al, 2020). Given that the unique methylation landscape of cancer DNA has been recently described to drive its preferential self-assembly onto metal surfaces (Sina et al, 2018), we thought that this phenomenon can be exploited for analyzing the cancerassociated DNA methylation landscape based on SERS. Starting from this hypothesis, we have recently demonstrated that SERS spectra of DNA from patients with acute leukemia (AL) exhibits a decreased intensity in the SERS band at 1005 cm−1 attributed to 5-methylcytosine compared to the DNA of control subjects, allowing a rapid and efficient differentiation between the two groups (Moisoiu et al, 2019). Other epigenetic changes of DNA bases previously described in cancer (acetylation, hydroxymethylation, etc.) have been reported only for synthetic DNA bases (Barhoumi and Halas, 2011)

Methods

Results

Conclusion