Capture-Based Targeted Ultradeep Sequencing in Paired Tissue and Plasma Samples Demonstrates Differential Subclonal ctDNA-Releasing Capability in Advanced Lung Cancer

Mao, Xiaowei; Zhang, Zhou; Zheng, Xiaoxuan; Xie, Fangfang; Duan, Feidie; Jiang, Liyan; Chuai, Shannon; Han‐Zhang, Han; Han, Baohui; Sun, Jiayuan

doi:10.1016/j.jtho.2016.11.2235

Cited by 112 publications

(122 citation statements)

References 31 publications

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“…[19] Size, status, and characteristics of cancerous tissues are also highly related. For example, when considering intratumor heterogeneity, subclones carrying driver mutations are more prone to release DNA [20]. However, some researches [21] in non-small cell lung cancer (NSCLC) have indicated that the cfDNA level is correlated with tumor metabolism and reflects tumor biological behaviors rather than tumor burden, potentially because nontumor DNA is also increased during tumor progression due to interactions between tumor cells and adjacent healthy tissue cells [22].…”

Section: Origin Of Ctdnamentioning

confidence: 99%

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

Zhang

Liang

et al. 2019

Mol Cancer

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Peripheral circulating free DNA (cfDNA) is DNA that is detected in plasma or serum fluid with a cell-free status. For cancer patients, cfDNA not only originates from apoptotic cells but also from necrotic tumor cells and disseminated tumor cells that have escaped into the blood during epithelial-mesenchymal transition. Additionally, cfDNA derived from tumors, also known as circulating tumor DNA (ctDNA), carries tumor-associated genetic and epigenetic changes in cancer patients, which makes ctDNA a potential biomarker for the early diagnosis of tumors, monitory and therapeutic evaluations, and prognostic assessments, among others, for various kinds of cancer. Moreover, analyses of cfDNA chromatin modifications can reflect the heterogeneity of tumors and have potential for predicting tumor drug resistance.

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Section: Origin Of Ctdnamentioning

confidence: 99%

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

Zhang

Liang

et al. 2019

Mol Cancer

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“…Cell-free DNA was extracted as described. 7 In brief, 10 mL of whole blood was collected and cell-free DNA was extracted from plasma samples by using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions.…”

Section: Preparation Of Plasma Cell-free Dnamentioning

confidence: 99%

“…Library preparation was performed as described. 7 Fragments with a size of 200 to 400 base pairs were selected and followed by hybridization with capture probes baits, hybrid selection with magnetic beads, and polymerase chain reaction (PCR) amplification. Indexed samples were sequenced on a Nextseq500 sequencer (Illumina, Inc., San Diego, CA) with paired-end reads.…”

Section: Next-generation Sequencing Library Preparationmentioning

confidence: 99%

Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance

Wang

Yang

Huang

et al. 2017

Journal of Thoracic Oncology

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“…The NGS library was prepared as described previously (29). Briefly, nucleotide fragments of 200-400 base pairs were selected using Agencourt AMPure beads (Beckman Coulter, Inc.).…”

Section: Next Generation Sequencing (Ngs) Library Preparation and Seqmentioning

confidence: 99%

Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity

Tang

Liu

et al. 2019

Oncol Lett

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Personalized medicine is revolutionizing the diagnosis and treatment of cancer; however, for personalized medicine to be used accurately, patient information is essential to determine the appropriate diagnosis, prognosis and treatment. The detection of genomic mutations in liquid biopsy samples is a non-invasive method of characterizing the genotype of a tumor. However, next generation sequencing-based plasma genotyping only has a sensitivity of ~70%. Identifying potential indicators that may reflect the sensitivity of a liquid biopsy analysis could offer important information for its clinical application. In the present study, 47 pairs of patient-matched plasma and tumor tissue samples obtained from patients with advanced lung cancer were sequenced using a panel of 56 cancer-associated genes. The plasma maximum allele frequency (Max AF) was identified as a novel biomarker to indicate the sensitivity of plasma genotyping. Using the identified somatic mutations in patient tissue biopsy samples as a reference, the sensitivity of the corresponding patient plasma test was investigated. The by-variant sensitivity of the plasma test was 68.1%, with 79 matched and 37 missed genetic aberrances. The by-patient sensitivity was calculated as 83%. Patients with a high plasma Max AF value (>2.2%) demonstrated a higher concordance with the range of mutations identified in the patient-matched tissue samples. The Max AF observed in patient plasma samples was positively correlated with liquid biopsy sensitivity and could be used as a potential indicator of liquid biopsy sensitivity. Therefore, patients with a low plasma Max AF (≤2.2%) may need to undergo further tissue biopsy to allow personalized oncology treatment. In summary, the present study may offer a non-invasive testing method for a subgroup of patients with advanced lung cancer.

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Capture-Based Targeted Ultradeep Sequencing in Paired Tissue and Plasma Samples Demonstrates Differential Subclonal ctDNA-Releasing Capability in Advanced Lung Cancer

Abstract: We have demonstrated that subclones carrying driver mutations are more prone to release DNA. We have also demonstrated the quantitative ability of capture-based sequencing, paving its way for routine utilization in clinical settings.

Cited by 112 publications

References 31 publications

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance

Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity

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