Liquid biopsy using the supernatant of a pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients: a comparison between cell-free DNA and extracellular vesicle-derived DNA

Lee, Jong Sik; Hur, Jae Young; Kim, In Ae; Kim, Hee Joung; Choi, Chang; Lee, Jae Chol; Kim, Wan Seop; Lee, Kye Young

doi:10.1186/s12885-018-5138-3

Cited by 67 publications

(71 citation statements)

References 26 publications

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“…T790M mutation was detected in urine and relevant tumor tissue from patients with NSCLC undergoing TKI therapy [24]. Using extracellular vesicle-derived DNA and ctDNA from pleural fluid supernatants yielded significant improvement in EGFR mutation analysis compared to the use of cell blocks or smears [54]. Kawahara et al [55] also detected EGFR mutations in four of 18 cytologically negative groups using pleural fluid supernatant ctDNA.…”

Section: Future Perspectives On Circulating Tumor Dna Testing In Lungmentioning

confidence: 99%

Current status and future perspectives of liquid biopsy in non-small cell lung cancer

Chang

Hur

Choi

et al. 2020

J Pathol Transl Med

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Molecular analysis is traditionally performed on tumor tissue. Although the number of mandatory tests for treatment decisions increases in patients with advanced non-small cell lung cancer (NSCLC), it is difficult to secure adequate tumor tissue for this purpose [1]. Small biopsy specimens, cell blocks, or aspirates are often the only available samples in patients with advanced NSCLC [2,3]. It is difficult to repeat tissue biopsies because they are invasive. Liquid biopsy could be an alternative or a complementary minimally invasive method for detecting molecular changes in NSCLC [1,2,4,5]. The clinical use of liquid biopsy to select patients with advanced NSCLC who are candidates for third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy has been demonstrated in many clinical trials [6-10]. The United States Food and Drug Administration (FDA) approved Cobas EGFR Mutation Test v2 (Roche, Indianapolis, IN, USA) in 2018 as a companion diagnostic for third-generation EGFR TKI based on these results [11]. The Korea National Health Insurance Service (NHIS) has covered circulating cell-free tumor DNA (ctDNA) tests for EGFR mutations in advanced NSCLC since 2018. In this review, we present the current status and future perspectives of liquid biopsy in patients with NSCLC. BIOLOGY OF CIRCULATING TUMOR DNA Liquid biopsy refers to the collection and analysis of analytes from various body fluids such as blood, urine, sputum, and pleural fluid [12-14]. Different analytes can be present in a liquid biopsy including circulating tumor cells (CTCs), circulating cell-free DNAs (cfDNAs), circulating tumor RNAs (ctRNAs), circulating exosomes, tumor-educated platelets, proteins, and metabolites [15,16]. CTCs are intact, viable tumor cells circulating in the blood [12]. Cancer releases single or clusters of CTCs into the bloodstream during the course of hematogenous spread. cfDNA refers to all circulating DNA in body fluids. cfDNA can be derived from neoplastic as well as non-neoplastic cells [15,16]. cfDNA can be detected in other body fluids, including urine, saliva, or cerebrospinal fluid. ctDNA refers to a subgroup

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Section: Future Perspectives On Circulating Tumor Dna Testing In Lungmentioning

confidence: 99%

Current status and future perspectives of liquid biopsy in non-small cell lung cancer

Chang

Hur

Choi

et al. 2020

J Pathol Transl Med

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“…Therefore, determining the original EGFR mutation status and monitoring the changes in mutations is crucial to the management of NSCLC, but biopsies are invasive procedures and can be technically impossible in some patients. So far, the concept of liquid biopsy has expanded from blood‐based resources to urine, saliva, effusion, cerebrospinal fluid and other body fluid, which acts as a simple, fast and cost efficient alternative for monitoring of disease status, or response to treatment in multiple malignancies, including lung cancer . A milestone is the approval for Cobas EGFR Mutation Test v2 (cobas, Roche Diagnostic US, Indianapolis, IN, USA) by the United States Food and Drug Administration (US FDA) in 2016.…”

Section: Introductionmentioning

confidence: 99%

“…So far, the concept of liquid biopsy has expanded from blood-based resources to urine, saliva, effusion, cerebrospinal fluid and other body fluid, which acts as a simple, fast and cost efficient alternative for monitoring of disease status, or response to treatment in multiple malignancies, including lung cancer. [14][15][16][17][18][19][20] A milestone is the approval for Cobas EGFR Mutation Test v2 (cobas, Roche Diagnostic US, Indianapolis, IN, USA) by the United States Food and Drug Administration (US FDA) in 2016. Compared with traditional tissue biopsy, liquid biopsy has many advantages such as speediness and convenience, and liquid biopsy technology can be used as an effective supplement for routine tissue biopsy in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Detection of EGFR gene mutation status from pleural effusions and other body fluid specimens in patients with lung adenocarcinoma

Zhang

Tang

et al. 2019

Thoracic Cancer

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Background Epidermal growth factor receptor (EGFR) gene mutation status is essential to the optimal management of lung adenocarcinoma. Liquid biopsy has advantages such as noninvasiveness, speediness, and convenience. This study aimed to detect EGFR gene mutations using next‐generation sequencing (NGS) from different types of body fluids from patients with lung adenocarcinoma. Methods This was a prospective study of 20 patients with lung adenocarcinoma recruited between January 2017 and December 2018 at the Beijing Hospital. All patients had adenocarcinoma with confirmed sensitizing EGFR mutations. Body fluid specimens included pleural effusion, ascites, pericardial effusion, and cerebrospinal fluid. NGS was conducted to test for nine lung cancer‐related gene in body fluid supernatant free DNA, sedimentary tumor cells, and plasma free DNA. Results The EGFR gene mutation abundance of body fluid supernatant free DNA was higher than that of body fluid sedimentary tumor cells and plasma free DNA specimens (100% vs. 90% vs. 80%, respectively, all P < 0.05). The results of EGFR mutation from the body fluid supernatants were consistent with the results from the tissue biopsy. Conclusions This study showed that compared with body fluid sediment tumor cells and plasma free DNA samples, body fluid supernatant free DNA has a higher detection rate and sensitivity of tumor‐specific mutations. Free DNA obtained from body fluid supernatants could be used as high‐quality specimens for gene mutation detection in patients with lung cancer. This could be applied in treatment decisions and patient management.

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“…One of the biggest drawbacks of direct sequencing vs was to detect mutations using cell free DNA. 28 Lin et al have shown that EGFR mutations can be detected in the supernatant, cell pellets of the pleural effusion using high resolution melting analysis and Sanger sequencing. 29 When implemented on a small pilot-scale study (n = 9), we were successful in detecting EGFR mutations in 5/9 (55%) subjects.…”

Section: Discussionmentioning

confidence: 99%

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC

et al. 2020

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Background: Lung cancer is the cause of a fourth of all cancer-related deaths. About a third of all lung adenocarcinoma tumours harbour mutations on exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene. Detection of these mutations allows for targeted therapies in the form of EGFR Tyrosine kinase inhibitors. Recently, "liquid biopsies" have emerged as an alternative to conventional tissue mutation detection. Aim: In this pilot study, we attempted to optimize EGFR mutation detection from malignant pleural effusions (MPEs) as "liquid biopsies" when tissue biopsies were unavailable. Resulting mutations were then to be mapped on the EGFR gene and explored using cBioPortal, a public cancer genomic database. Methods and results: We first attempted a direct sequencing approach and showed that single nucleotide variants (SNVs) were likely to be missed in MPEs. We then switched to and optimized an EGFR mutant-specific quantitative polymerase chain reaction-based assay. This assay was piloted on n = 10 pleural effusion samples (one non-malignant pleural effusion as a negative control). 5/9 (55.55%) samples harboured EGFR mutations with 2/9 (22.22%) being exon 19 deletions and 3/9 (33.33%) the S768I mutation. The frequency of the S768I SNV in our study was significantly higher than that observed in other studies (0.2%). Utilizing cBioPortal data, we report that patients with S768I have a shorter median survival time (6 months vs 38 months), progression-free survival time (8 months vs 44 months) and lower tumor mutation count compared to patients with other EGFR mutations. Conclusions: The shorter survival of patients with the S768I SNV predicts aggressive disease and poor prognosis as a result of this mutation. Studies in larger cohorts and/or animal models are necessary to confirm these findings.

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Liquid biopsy using the supernatant of a pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients: a comparison between cell-free DNA and extracellular vesicle-derived DNA

Cited by 67 publications

References 26 publications

Current status and future perspectives of liquid biopsy in non-small cell lung cancer

Current status and future perspectives of liquid biopsy in non-small cell lung cancer

Detection of EGFR gene mutation status from pleural effusions and other body fluid specimens in patients with lung adenocarcinoma

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC

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