Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements
Abstract
:1. Introduction
2. NGS, ddPCR, and Liquid Biopsy for ctDNA Analysis
3. Epigenetic Modifications of Circulating DNA May Reflect Tissue Origin of an Unknown Primary Cancer
4. Circulating DNA as a Prognostic Criterion in Oncology
5. Circulating Tumor DNA Analysis for Cancer Personalized Medicine
6. Circulating DNA in Glioma Diagnosis
7. Urinary Circulating DNA in Urological Tumors
8. Multiplex Genotyping Based on ctDNA Mass-Spectrometry
9. Limitations of the Use of ctDNA in Cancer Routine Practice
- The majority of patients in the study had stage II–III of disease, which does not yet provide an opportunity to assess the applicability of the test for early diagnosis [232].
- As control, the authors analyzed the urine of only healthy individuals. Thus, the high specificity of the CancerSeek approach requires further validation with non-cancer control with associated diseases, such as inflammatory diseases of the genitourinary system, which are common in the elderly [233].
- The limitations of the method are linked with the same heterogeneity of tumors, such as lung cancer [234]. These circumstances cannot be attributed to the shortcomings of the method, but make it necessary to add additional markers that may increase the accuracy of the study, such as RNA of exosomes for early diagnosis of non-small cell lung cancer [235].
10. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics and Scope | Liquid Biopsy | Tissue Biopsy |
---|---|---|
Invasiveness | Minimally invasive | Invasive |
Study prescription time | On demand repeatedly | Prior a therapy prescription |
Sample degradation | No, long keeping in −70 °C [35] | Cross-linking and DNA fragmentation [35] |
Tumor size/number of tumor cells for detectable ctDNA | 5 × 107 cells [9] | >109 cells [9] |
Amount of biomaterial | 3 mL peripheral venous blood | Depending on the technique and organ |
Screening | Yes [36] | No |
Therapy choice | Yes | Yes |
Continuous dynamic observation (monitoring) | Yes, half-life of ctDNA between 16 min and 13 h [32,33,34] | No, too traumatic |
Response to therapy | Yes [21,34] | No |
Residual tumors | Yes [21,34] | No |
Relapse prognosis | Yes [21,34] | No |
Purpose of Research | Method | Example of Application | Specimen | Sensitivity Specificity % |
---|---|---|---|---|
Early diagnostics, screening | Target Deep Sequencing -TamSeq | Ovaries cancer (EGFR, TP53 *) [45] | Plasma | >97/>97 |
Target Deep Sequencing -Ion-AmpliSeq (Ion Torrent) | Breast cancer (p53, PIK3CA, PTEN, AKT1, IDH2, SMAD4) [27] | Plasma | n/a | |
Target Deep Sequencing by Illumina- Hi-Seq | Pancreatobiliary Carcinomas (KRAS, TP53, APC, FBXW7, SMAD4) [46] | Plasma | >92/100 | |
Massively Parallel Sequencing - CancerSEEK | Eight types of cancer (ovaries, liver, stomach, pancreas, esophagus, rectum, lungs and breast) [36] | Plasma | On average 70/>99 | |
Quantitative Methylation Specific PCR | BC (POU4F2 и PCDH17)7; BC (TWIST1 и NID2) [47,48,49] | Urine | 90/94 90/93 | |
The liquid typing on microspheres | Gliomas WHO I-IV (The level of Alu methylation) [50] | Plasma | n/a | |
HPLC ESI-MS-SOMA | HCC (p53) [51] | Plasma | n/a | |
Identification of cancers of unknown primary | Target Deep Sequencing by Illumina- Hi-Seq or Next-Seq | SCLC, squamous cell lung cancer, colorectal adenocarcinoma, HCC and duct carcinoma of the mammary gland in situ [22] | Plasma | n/a |
Detection of minimal residual tumor | ddPCR-CNVs | Breast cancer (USP17L2 (DUB3), BRF1, MTA1, and JAG2) [52] | Plasma | n/a |
Metastasis detection | ddPCR-CNVs | Breast cancer [53] Gastric cancer (MET, HER2) [54,55] | Plasma | 93/100 73.3/93.3 |
Target Deep Sequencing -TamSeq | Breast cancer (PIK3CA, TP53) [37] | Plasma | n/a | |
Integral tumor profiling in each specific patient | Massively Parallel Sequencing-PARE + PCR | Specific somatic rearrangements in the chromosomal DNA of solid tumors and plasma ** [56,57] | Tumor tissue + Plasma | n/a |
Target Deep Sequencing - CAPP-Seq | NSCLC [25,58] | Plasma | 85/96 *** | |
MALDI-TOF-MS | NSCLC (EGFR, KRAS, BRAF, ALK, PIK3CA, ERBB2, DDR2, AKT, and MEK1) [59] | Tumor tissue + Plasma | n/a | |
Monitoring of therapy effectiveness and clinical prognosis | Target Deep Sequencing -Tam-Seq and genome-wide sequencing | Invasive bladder muscle cancer [60] | Urine | 83/100 |
Diagnostics, screening, monitoring etc | ddPCR-SNP and chromosome rearrangement | Different tumor types (PIK3CA KRAS, BRAF, NRAS, and EGFR) ** [31,61,62] | Plasma | 87.2/99.2 |
Molecular Target | Sample Type | Technology | Study(ies) |
---|---|---|---|
Non-Small Cell Lung Carcinoma | |||
EGFR mutation | ctDNA | ddPCR | [177] |
ctDNA | ddPCR | [178] | |
CTCs | NGS | [179] | |
PD-L1 expression | CTCs | Immunofluorescence | [180] |
ctRNA | qPCR | [175] | |
CTCs | Immunofluorescence | [181] | |
Colorectal Cancer | |||
APC mutation | ctDNA | NGS | [172] |
CTCs | NGS | [182] | |
ctDNA | ddPCR | [183] | |
KRAS mutation | ctDNA | COLD PCR, Microarray, ddPCR | [184] |
ctDNA | NGS | [185] | |
ctDNA | ddPCR | [139] | |
CTCs | Nested PCR | [186] | |
BRAF mutation | ctDNA | PCR-Microarray | [187] |
ctDNA | ddPCR | [188] | |
CTCs | qPCR | [189] | |
mSEPT9 methylation | ctDNA | Real-Time PCR | [190] |
Breast Cancer | |||
HER2 expression | ctDNA | NGS | [191] |
CTCs | Immunofluorescence | [192] | |
PD-L1 expression | ctRNA | qPCR | [175] |
CTCs | Western blot Flow Cytometry Immunocytochemistry | [193] | |
PIK3CA mutation | ctDNA | ddPCR | [176] |
ctDNA | NGS | [194] | |
ctDNA | NGS | [195] | |
CTCs | ddPCR | [134] | |
Cutaneous Melanoma | |||
BRAF mutation | ctDNA | ddPCR | [126] |
CTCs | ddPCR | [196] | |
ctDNA | Exome NGS | [197] | |
PTEN mutation | ctDNA | SNPase-ARMS qPCR | [198] |
CTCs | NGS RNA | [199] | |
TERT promoter mutation | ctDNA | ddPCR | [200] |
KIT mutation | ctDNA | NGS | [201] |
CTCs | hemi-nested PCR | [202] |
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Share and Cite
Tuaeva, N.O.; Falzone, L.; Porozov, Y.B.; Nosyrev, A.E.; Trukhan, V.M.; Kovatsi, L.; Spandidos, D.A.; Drakoulis, N.; Kalogeraki, A.; Mamoulakis, C.; Tzanakakis, G.; Libra, M.; Tsatsakis, A. Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements. Cells 2019, 8, 1251. https://doi.org/10.3390/cells8101251
Tuaeva NO, Falzone L, Porozov YB, Nosyrev AE, Trukhan VM, Kovatsi L, Spandidos DA, Drakoulis N, Kalogeraki A, Mamoulakis C, Tzanakakis G, Libra M, Tsatsakis A. Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements. Cells. 2019; 8(10):1251. https://doi.org/10.3390/cells8101251
Chicago/Turabian StyleTuaeva, Natalia O., Luca Falzone, Yuri B. Porozov, Alexander E. Nosyrev, Vladimir M. Trukhan, Leda Kovatsi, Demetrios A. Spandidos, Nikolaos Drakoulis, Alexandra Kalogeraki, Charalampos Mamoulakis, George Tzanakakis, Massimo Libra, and Aristides Tsatsakis. 2019. "Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements" Cells 8, no. 10: 1251. https://doi.org/10.3390/cells8101251