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Page 6 of 8 Moia et al. J Cancer Metastasis Treat 2019;5:67 I http://dx.doi.org/10.20517/2394-4722.2019.020

CONCLUSIONS AND FUTURE PERSPECTIVES
In conclusion, liquid biopsy is a non-invasive method that may be used in lymphomas to achieve several
objectives: (1) better characterize the biology and pathogenesis of the lymphoma through the analysis of
biological markers that reflect the entire molecular heterogeneity of the disease in its different anatomical
sites; (2) identify new prognostic and predictive markers; and (3) prospectively evaluate the dynamics of
ctDNA during treatment in order to predict the probability of response to treatment in a more sensitive
and specific manner and, if necessary, the need for an early switch to a more efficacious treatment. In order
to validate these initial results, several ongoing clinical trials aim at assessing whether cfDNA genotyping
can improve outcome prediction in lymphoid malignancies and whether it might identify mutations
[29]
[28]
[30]
predisposing to treatment resistance (NCT03280394 , NCT02883517 , NCT03702309 ).
In addition to the previously mentioned application of liquid biopsy in lymphoma, preliminary evidence
also suggests that cfDNA analysis might reflect the methylation profile identified in the tissue biopsy [31,32] .
More precisely, global hypomethylation of the genome, as well as aberrant methylation of specific regions
of interest detected on the liquid biopsy, namely DAPK1 promoter hypermethylation, might represent
potential prognostic biomarkers in lymphomas [31,32] .

The liquid biopsy of lymphoma, as described in this review, aims at analysing mutations of somatic origin,
and therefore does not pose major ethical issues beyond the conventional ethical requirements. If the
patient plasma is stored in a biobank for subsequent analysis, the conventional guidelines for biobanking
should be followed [33,34] .

DECLARATIONS
Authors’ contributions
Writing, reviewing and editing the manuscript: Moia R, Favini C, Rasi S, Deambrogi C, Ferri V, Schipani M,
Sagiraju S, Mokhtar Mahmoud A, Kodipad AA, Adhinaveni R, Patriarca A, Nassi L, Gaidano G

Availability of data and materials
Not applicable.

Financial support and sponsorship
Work by the authors described in this review has been supported by Molecular bases of disease
dissemination in lymphoid malignancies to optimize curative therapeutic strategies, (5 ´ 1000 No. 21198),
Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy; Progetto Ricerca Finalizzata RF-
2011-02349712, Ministero della Salute, Rome, Italy; PRIN 2015ZMRFEA_004, MIUR, Rome, Italy; and
AGING Project - Department of Excellence - DIMET, Università del Piemonte Orientale, Novara, Italy.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.