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SERS assessment of the cancer-specific methylation pattern of genomic DNA: towards the detection of acute myeloid leukemia in patients undergoing hematopoietic stem cell transplantation
Authors:Moisoiu  Vlad  Stefancu  Andrei  Iancu  Stefania D  Moisoiu  Tudor  Loga  Luminita  Dican  Lucia  Alecsa  Cristian D  Boros  Imre  Jurj  Anca  Dima  Delia  Bagacean  Cristina  Tetean  Romulus  Burzo  Emil  Tomuleasa  Ciprian  Elec  Florin  Leopold  Nicolae
Institution:1.Faculty of Physics, Babeș-Bolyai University, Kogalniceanu 1, 400084, Cluj-Napoca, Romania
;2.Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Victor Babeș 8, 400349, Cluj-Napoca, Romania
;3.Clinical Institute of Urology and Renal Transplant, Clinicilor 2, 400006, Cluj-Napoca, Romania
;4.Department of Biochemistry, Iuliu Hatieganu University of Medicine and Pharmacy, Pasteur 6, 400349, Cluj-Napoca, Romania
;5.Faculty of Mathematics and Computer Science, Babeș-Bolyai University, Ploiești 22-25, 400084, Cluj-Napoca, Romania
;6.Tiberiu Popoviciu Institute of Numerical Analysis, Fantanele 57, 400320, Cluj-Napoca, Romania
;7.Research Center for Functional Genomics and Translational Medicine/Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Marinescu 23, 400337, Cluj Napoca, Romania
;8.Department of Hematology, Ion Chiricuta Clinical Cancer Center, Bvd. 21 Decembrie 1989 73, 400124, Cluj-Napoca, Romania
;9.INSERM UMR1227, B Lymphocytes and Autoimmunity, University Bretagne Occidentale, Foch Avenue 5, 29609, Brest, France
;10.Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Bvd. 21 Decembrie 1989 73, 400124, Cluj-Napoca, Romania
;11.Department of Urology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 2, 400139, Cluj-Napoca, Romania
;
Abstract:

In this label-free surface-enhanced Raman scattering (SERS) study of genomic DNA, we demonstrate that the cancer-specific DNA methylation pattern translates into specific spectral differences. Thus, DNA extracted from an acute myeloid leukemia (AML) cell line presented a decreased intensity of the 1005 cm−1 band of 5-methylcytosine compared to normal DNA, in line with the well-described hypomethylation of cancer DNA. The unique methylation pattern of cancer DNA also influences the DNA adsorption geometry, resulting in higher adenine SERS intensities for cancer DNA. The possibility of detecting cancer DNA based on its SERS spectrum was validated on peripheral blood genomic DNA samples from n = 17 AML patients and n = 17 control samples, yielding an overall classification of 82% based on the 1005 cm−1 band of 5-methylcytosine. By demonstrating the potential of SERS in assessing the methylation status in the case of real-life DNA samples, the study paves the way for novel methods of diagnosing cancer.

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