PDF
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.
Conclusion: We showed that the clonal evolution of tumors includes a private combination of genes, regardless of tumor type. In the future, the cancer treatment can be the targeted therapy against specific tumor mutation(s). The present approach seems promising to both identify key cancer genes and follow clonal evolution over time.
Keywords
Cell-free DNA
/
liquid biopsy
/
solid tumors
/
advanced tumors
/
private mutations
/
targeted-therapy
Cite this article
Download citation ▾
Maria Palmieri, Margherita Baldassarri, Nicola Iuso, Francesca Fava, Alessandra Fabbiani, Francesco Cetta, Chiara Fallerini, Rossella Tita, Maria Antonietta Mencarelli, Alessandra Renieri, Elisa Frullanti.
Private somatic mutations identified with liquid biopsy lead tumor progression in solid cancers.
Journal of Cancer Metastasis and Treatment, 2020, 6: 55 DOI:10.20517/2394-4722.2020.105
| [1] |
Weinstein IB.Oncogene addiction..Cancer Res2008;68:3077-80
|
| [2] |
Mader S.Liquid biopsy: current status and future perspectives..Oncol Res Treat2017;40:404-8
|
| [3] |
Merlo LM,Reid BJ.Cancer as an evolutionary and ecological process..Nat Rev Cancer2006;6:924-35
|
| [4] |
Greaves M.Clonal evolution in cancer..Nature2012;481:306-13 PMCID:PMC3367003
|
| [5] |
Palmieri M,Fava F.Two-point-NGS analysis of cancer genes in cell-free DNA of metastatic cancer patients..Cancer Med2020;9:2052-61 PMCID:PMC7064095
|
| [6] |
Braun S,Sommer HL.Tumor-antigen heterogeneity of disseminated breast cancer cells: implications for immunotherapy of minimal residual disease..Int J Cancer1999;84:1-5
|
| [7] |
Ilié M.Pros: can tissue biopsy be replaced by liquid biopsy?.Transl Lung Cancer Res2016;5:420-3 PMCID:PMC5009092
|
| [8] |
Gerlinger M,Horswell S.Intratumor heterogeneity and branched evolution revealed by multiregion sequencing..N Engl J Med2012;366:883-92 PMCID:PMC4878653
|
| [9] |
Li BT,Chaft JE.Liquid biopsy for ctDNA to revolutionize the care of patients with early stage lung cancers..Ann Transl Med2017;5:479 PMCID:PMC5733322
|
| [10] |
Rossi G,Rademaker AW.Cell-free DNA and circulating tumor cells: comprehensive liquid biopsy analysis in advanced breast cancer..Clin Cancer Res2018;24:560-8
|
| [11] |
Li H,Wang L.PIK3CA mutations mostly begin to develop in ductal carcinoma of the breast..Exp Mol Pathol2010;88:150-5
|
| [12] |
Samuels Y,Schmidt-Kittler O.Mutant PIK3CA promotes cell growth and invasion of human cancer cells..Cancer Cell2005;7:561-73
|
