Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma

Rachiglio, Anna Maria; Abate, Riziero Esposito; Sacco, Alessandra; Pasquale, Raffaella; Fenizia, Francesca; Lambiase, Matilde; Morabito, Alessandro; Montanino, Agnese; Rocco, Gaetano; Romano, Carmen; Nappi, Anna; Iaffaioli, Rosario Vincenzo; Tatangelo, Fabiana; Botti, Gerardo; Ciardiello, Fortunato; Maiello, Monica R.; Luca, Antonella De; Normanno, Nicola

doi:10.18632/oncotarget.10704

Cited by 79 publications

(83 citation statements)

References 33 publications

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“…As NGS is currently becoming routine for tumor tissue profiling, different assays (eg, AmpliSeq Cancer Panel, Thermo Fisher; RAS Panel, Illumina) are validated for clinical applications but have limited analytical sensitivities for ctDNA diagnostics. For example, in a proof‐of‐concept study, the FDA‐approved Oncomine targeted sequencing kit demonstrated a sensitivity of only 77% for the detection of sensitizing EGFR mutations in cfDNA of NSCLC patients . Similar results, with an overall concordance of 76% between tumor tissue and cfDNA, were reported for the AmpliSeq Cancer Panel .…”

Section: Different Methods For Mutation Detection In Routine Diagnosticssupporting

confidence: 53%

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

162

151

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Recently, many genome-wide profiling studies provided insights into the molecular make-up of major cancer types. The deeper understanding of these genetic alterations and their functional consequences led to the discovery of novel therapeutic opportunities improving clinical management of cancer patients. While tissue-based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are invasive sampling procedures carrying the risk of complications and may not represent the entire tumor due to underlying genetic heterogeneity. In this context, complementary characterization of genetic information in the blood of cancer patients can serve as minimal-invasive 'liquid biopsy'. Fragments of circulating cell-free DNA (cfDNA) are released from tissues of healthy individuals as well as cancer patients. The fraction of cfDNA that is released from primary tumors or metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in cancer cells, which are a potential source for diagnostic, prognostic, and predictive biomarkers. Recent studies have demonstrated technical feasibility and clinical applications including detection of drug targets and resistance mutations as well as longitudinal monitoring of tumors under therapy. To this end, a variety of pre-analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR-based single locus assays to genome-wide approaches are available, which considerably differ in sensitivity, specificity, and throughput. However, broad implementation of ctDNA analysis in daily clinical practice requires a thorough understanding of theoretical, technical, and biological concepts and necessitates standardization and validation of pre-analytical and analytical procedures across different technologies. Here, we review the pertinent literature and discuss the advantages and limitations of available methodologies and their potential applications in molecular diagnostics.

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Section: Different Methods For Mutation Detection In Routine Diagnosticssupporting

confidence: 53%

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

162

151

View full text Add to dashboard Cite

show abstract

“…Increasing evidence shows that the majority of solid tumors, including NSCLC, are highly heterogeneous (60,61). As a consequence of such intra-tumor heterogeneity, also driver mutations might be subclonal in selected patients (60,62,63). Evidence also suggests that the tumor heterogeneity is likely to increase over the time with the different lines of therapy.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Clinical utility of circulating tumor cells in patients with non-small-cell lung cancer

Gallo

Luca

Maiello

et al. 2017

Transl. Lung Cancer Res.

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Several different studies have addressed the role of the circulating tumor cells (CTC) in nonsmall-cell lung cancer (NSCLC). In particular, the potential of CTC analysis in the early diagnosis of NSCLC and in the prediction of the outcome of patients with early and advanced NSCLC have been explored. A major limit of these studies is that they used different techniques for CTC isolation and enumeration, they employed different thresholds to discriminate between high-and low-risk patients, and they enrolled heterogeneous and often small cohort of patients. Nevertheless, the results of many studies are concordant in indicating a correlation between high CTC count and poor prognosis in both early and advanced NSCLC. The reduction of CTC number following treatment might also represent an important indicator of sensitivity to therapy in patients with metastatic disease. Preliminary data also suggest the potential for CTC analysis in the early diagnosis of NSCLC in high-risk individuals. However, these findings need to be confirmed in large prospective trials in order to be transferred to the clinical practice.The molecular profiling of single CTC in NSCLC might provide important information on tumor biology and on the mechanisms involved in tumor dissemination and in acquired resistance to targeted therapies. In this respect, xenografts derived from CTC might represent a valuable tool to investigate these phenomena and to develop novel therapeutic strategies.

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“…Rachiglio et al [95] recently showed that, in CRC patients, the sensitivity of the NGS plasma analysis for RAS mutations was 100% in patients without resection of the primary tumour before blood collection, and 46.2% in patients with primary tumour resected before enrollment. Their results suggest the importance of identifying specific clinical characteristics to help select patients with sufficient levels of ctDNA for plasma NGS analysis.…”

Section: Resultsmentioning

confidence: 99%

Liquid Biopsies for Monitoring Temporal Genomic Heterogeneity in Breast and Colon Cancers

et al. 2017

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Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the “liquid biopsy” was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term “liquid biopsy” generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer. The implementation and standardization of both approaches are still needed to achieve the required sensitivity and specificity to successfully analyze heterogenous tumours, but pivotal studies, in particular those concerning colorectal cancer, have shown the feasibility and usefulness of liquid biopsy for monitoring the Darwinian clonal evolution from an early to a metastatic stage.

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Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma

Cited by 79 publications

References 33 publications

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Clinical utility of circulating tumor cells in patients with non-small-cell lung cancer

Liquid Biopsies for Monitoring Temporal Genomic Heterogeneity in Breast and Colon Cancers

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