The contribution of the 20<sup>th</sup> century discoveries on the circulating DNA as biomarkers for cancer screening

ALVES, GILDA; CHANTRE, MARIANA; DELMONICO, LUCAS

doi:10.1590/0001-3765202020200919

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BIOMEDICAL SCIENCES • An. Acad. Bras. Ciênc. 92 (4) • 2020 • https://doi.org/10.1590/0001-3765202020200919 copy

The contribution of the 20^th century discoveries on the circulating DNA as biomarkers for cancer screening

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Circulating DNA can be released in the biological fluids by a physiological process and by different pathological conditions. The first reports detecting circulating DNA in human plasma date from the late 40s. Even when specific pathological conditions were analyzed, the clinical importance of circulating DNA remained unclear. After PCR introduction, genetic and epigenetic alterations in circulating DNA gained more prominence for understanding the mechanisms of cancer development and progression. Nowadays, the circulating DNA assays are highlighted for their clinical relevance for cancer screening in liquid biopsy. In this review, we described the landscape of studies on circulating DNA isolated from human plasma or serum and the molecular tools used to obtain these findings throughout the 20th century and the current application in cancer.

Key words
Cancer; oncology; circulating DNA; liquid biopsy; plasma; serum

Year/Period	Observations	References
1948	Nucleic acids (P nuclei) is found in human plasma.	Mandel & Métais 1948.
1965	Circulating DNA can transform eukaryotic cells.	Bendich et al. 1965.
1966	Release of circulating DNA in serum of SLE patients.	Tan et al. 1966.
70s - 80s Characterization of circulating DNA	DNA release is normal and regulated. DNA is released in complexes. Cancerous cells release more circulating DNA than normal cells.	Rogers et al. 1972, Davis & Davis 1973, Olsen & Harris 1974, Anker et al. 1975, 1976, Leon et al. 1977, Stroun et al. 1977, 1987, Hoessli et al. 1977, Juckett & Rosenberg 1982, Shapiro et al. 1983, Steinman 1984.
90s Sequence specific studies	Screening of mutations in oncogenes and tumor, suppressor genes, microsatellites instability and DNA methylations in serum and plasma of cancer patients.	Koshland 1993, Peltomäki et al. 1993, Vasioukhin et al. 1994, Mao et al. 1994, Chen et al. 1996, Nawroz et al. 1996, Anker et al. 1997, Kopreski et al. 1997, Silva et al. 1999, Esteller et al. 1999.

Century	Methods
20^th	Immunologic techniques with DNA antibodies
	DNA isolation procedure by proteolysis and phenol extraction
	Ultracentrifugation
	DNA quantification by ultraviolet absorbance at 260nm
	Radioimmunoassay technique
	Counterimmunoelectrophoresis
	Chromatography
	Enzyme digestion: DNase, RNase, S1-endonuclease
	dsDNA, ssDNA and RNA radioactivity labelling
	Cell culture/Organ culture
	PCR, PCR-SSCP, MSP-PCR
	In-house DNA sequencing
21^st	Blood long-term preservation tubes
	Circulating DNA isolation kits
	Automatic DNA sequencing
	FDA approved tests: Cobas EGFR Mutation Test v2 (Roche) and the Epi proColon® (Epigenomics AG)
	Tests in development: FoundationOne® Liquid (Foundation Medicine), Guardant360® (Guardant), Grail Biotech and CancerSEEK (Thrive Earlier Detection Corp.)

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[1] Correspondence to: Gilda Alves E-mail: galvesbrown@gmail.com

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The contribution of the 20th century discoveries on the circulating DNA as biomarkers for cancer screening

Abstract

The contribution of the 20^th century discoveries on the circulating DNA as biomarkers for cancer screening