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Palmieri et al. J Cancer Metastasis Treat 2020;6:55 Journal of Cancer
DOI: 10.20517/2394-4722.2020.105 Metastasis and Treatment

Original Article Open Access

Private somatic mutations identified with liquid
biopsy lead tumor progression in solid cancers

Maria Palmieri , Margherita Baldassarri , Nicola Iuso , Francesca Fava 1,2,3 , Alessandra Fabbiani 1,2,3 ,
1,2
1,2
3
Francesco Cetta , Chiara Fallerini , Rossella Tita , Maria Antonietta Mencarelli , Alessandra Renieri 1,2,3 ,
3
1,2
1
3
Elisa Frullanti 1,2
1 Medical Genetics, University of Siena, Siena 53100, Italy.
2 Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena 53100, Italy.
3 Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena 53100, Italy.
Correspondence to: Prof. Alessandra Renieri, Medical Genetics Unit, University of Siena, Policlinico “Santa Maria alle Scotte”, 2
Viale Bracci, Siena 53100, Italy. E-mail: alessandra.renieri@unisi.it
How to cite this article: Palmieri M, Baldassarri M, Iuso N, Fava F, Fabbiani A, Cetta F, Fallerini C, Tita R, Mencarelli MA, Renieri
A, Frullanti E. Private somatic mutations identified with liquid biopsy lead tumor progression in solid cancers. J Cancer Metastasis
Treat 2020;6:55. http://dx.doi.org/10.20517/2394-4722.2020.105
Received: 23 Sep 2020 First Decision: 23 Nov 2020 Revised: 4 Dec 2020 Accepted: 21 Dec 2020 Published: 30 Dec 2020

Academic Editor: PRAVIN POTDAR Copy Editor: Monica Wang Production Editor: Jing Yu

Abstract
Aim: Primary tumors can be divided into oncogene-addicted (e.g., lung) and non-oncogene addicted (e.g., breast).
Only the former group has an Achilles-heel single gene for successful target therapy, whereas the latter has
mutations of multiple causative genes. Currently, tissue biopsy used for genetic surveys do not give a complete
picture of the molecular profile and clonal evolution, but only provide static information over time.

Methods: A series of 133 patients with 16 different solid tumors were enrolled. Blood samples were collected
and cell-free DNA (cfDNA) was extracted. cfDNA libraries were analyzed using AVENIO circulating tumor DNA
(ctDNA) Expanded Kit and Illumina NextSeq 550 for sequencing was used. In order to evaluate the clinical evolution
over time, a second cfDNA analysis was performed after a mean interval of 2 months.

Results: Through the cfDNA liquid biopsy, we found 89 pathogenic variants in 54 genes. Breast, lung, and prostate
cancers showed the largest number of mutated genes. TP53, PIK3CA, FGFR3, KRAS, and ERBB2 were the most
frequently mutated genes among 16 different tumors. Gene distribution didn’t show any type of prevalence. In
particular, every patient with disease progression seems to have a “private” combination of gene pair mutations,
with TP53 as the most frequently mutated gene.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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