Circulating free tumor DNA and colorectal cancer

Lecomte, Thierry; Cézé, Nicolas; Dorval, Étienne; Laurent‐Puig, Pierre

doi:10.1016/j.gcb.2009.04.015

Cited by 52 publications

(44 citation statements)

References 112 publications

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“…The cfDNA in plasma from patients with cancer originates from normal nonmalignant cells as well as necrotic and apoptotic tumor cells (21), but neither the origin nor fate of the circulating DNA is fully explored (18). A recent review has summarized the few older clinical studies in CRC, but although the results were promising, the studies were small and primarily based on pre/post-surgical measurements or comparison with healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

“…However, results have not been translated into clinical practice, but efforts during the last decade have led to significant progress in the development of highly sensitive and reproducible methods (17). The factors influencing the quantitative as well as qualitative changes of cell-free DNA (cfDNA) in patients with cancer are multiple and not yet fully explored, but a substantial proportion of circulating cfDNA in plasma is believed to originate from tumor cells and can, therefore, be tested for tumor-specific genetic alterations such as KRAS or BRAF mutations (18,19). Clearly, this opens up for investigations of a number of highly relevant issues such as methodology, correlation to clinical outcome, dynamic changes of mutational status during EGFR inhibitor treatment, and potential solutions of practical issues.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

Spindler

Pallisgaard

Vogelius

et al. 2012

Clinical Cancer Research

242

212

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Purpose: The present study investigated the levels of circulating cell-free DNA (cfDNA) in plasma from patients with metastatic colorectal cancer (mCRC) in relation to third-line treatment with cetuximab and irinotecan and the quantitative relationship of cfDNA with tumor-specific mutations in plasma.Experimental Design: Inclusion criteria were histopathologically verified chemotherapy-resistant mCRC, adequate Eastern Cooperative Oncology Group performance status, and organ function. Treatment consisted of irinotecan being administered at 350 mg/m 2 for 3 weeks and weekly administration of 250 mg/m 2 cetuximab until progression or unacceptable toxicity. A quantitative PCR method was developed to assess the number of cfDNA alleles and KRAS and BRAF mutation alleles in plasma at baseline. Results: The study included 108 patients. Only three patients were positive for BRAF mutations. The majority of KRAS mutations detected in tumors were also found in the plasma [32 of 41 (78%)]. Plasma cfDNA and plasma mutant KRAS levels (pmKRAS) were strongly correlated (r ¼ 0.85, P < 10 À4). The disease control rate was 77% in patients with low cfDNA (<25% quartile) and 30% in patients with high cfDNA [>75% quartile (P ¼ 0.009)]. Patients with pmKRAS levels higher than 75% had a disease control rate of 0% compared with 42% in patients with lower pmKRAS (P ¼ 0.048). Cox analysis confirmed the prognostic importance of both cfDNA and pmKRAS. High levels were clear indicators of a poor outcome.Conclusions: KRAS analysis in plasma is a viable alternative to tissue analysis. Quantitative levels of cfDNA and pmKRAS are strongly correlated and hold promise of clinical application.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

Spindler

Pallisgaard

Vogelius

et al. 2012

Clinical Cancer Research

242

212

View full text Add to dashboard Cite

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“…In addition, determination of universal thresholds and validation of the dPCR procedure for predicting the quality of sequencing data should be executed with substantially larger sample populations. Combined with screening for tumor markers in patient plasma samples (30 ), an assay for DNA integrity might also be valuable as a cancer biomarker (31 ) for diagnostics and patient follow-up.…”

Section: Sequencing Of Ffpe Samplesmentioning

confidence: 99%

Multiplex Picoliter-Droplet Digital PCR for Quantitative Assessment of DNA Integrity in Clinical Samples

Didelot

Kotsopoulos²,

Lupo

et al. 2013

Clinical Chemistry

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BACKGROUND: Assessment of DNA integrity and quantity remains a bottleneck for high-throughput molecular genotyping technologies, including nextgeneration sequencing. In particular, DNA extracted from paraffin-embedded tissues, a major potential source of tumor DNA, varies widely in quality, leading to unpredictable sequencing data. We describe a picoliter droplet-based digital PCR method that enables simultaneous detection of DNA integrity and the quantity of amplifiable DNA.

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“…Undoubtedly, DLC1 methylation plays an important role in CRC development, this study currently investigates the diagnostic role of DLC1 methylation in CRC. [23] . Enriched DNA makes it possible to detect tumor-specific DNA alteration in the peripheral blood of patients.…”

Section: Discussionmentioning

confidence: 99%

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

Zou

Tang

et al. 2011

Chin. J. Cancer Res.

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Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is to evaluate the diagnostic role of DLC1 gene methylation in the serum DNA from CRC patients.Methods: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed.Results: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls (8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients' clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. Conclusion:The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.

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Circulating free tumor DNA and colorectal cancer

Cited by 52 publications

References 112 publications

Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

Multiplex Picoliter-Droplet Digital PCR for Quantitative Assessment of DNA Integrity in Clinical Samples

Detection and clinical significance of DLC1 gene methylation in serum DNA from colorectal cancer patients

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