scholarly journals Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Ying-Chi Yang ◽  
Dong Wang ◽  
Lan Jin ◽  
Hong-Wei Yao ◽  
Jing-Hui Zhang ◽  
...  
Keyword(s):  
Late Stage ◽  
Gene Mutations ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Diagnosis And Treatment ◽  
Response To Treatment ◽  
Non Invasive ◽  
Patient Prognosis ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

Characterization, diagnosis, and treatment of colorectal cancers (CRC) is difficult due to limited biopsy information, impracticality of repeated biopsies, and cancer biomarker fallibility. Circulating tumor DNA (ctDNA) has recently been investigated as a non-invasive way to gain representative gene mutations in tumors, in addition to monitoring disease progression and response to treatment. We analyzed ctDNA mutations and concentrations in 47 early- and late-stage CRC patients using a targetted sequencing approach using a panel that covers 50 cancer-related genes. ctDNA mutations in 37 genes were identified in 93.6% of the patients (n=47). The results showed that TP53, PIK3CA, APC, and EGFR were the most frequently mutated genes. Stage IV patients had significantly higher ctDNA concentration than Stage I patients, and increased ctDNA concentration correlated with increased tumor size. Additionally, ctDNA detection was found to be a greater predictor of disease when compared with five known commonly used tumor biomarkers. The present study supports the use of ctDNA as a liquid biopsy to gain clinical tumor information that may facilitate early diagnosis and treatment and improve CRC patient prognosis.

scholarly journals Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis

2017 ◽  
Vol Volume 10 ◽  
pp. 945-953 ◽  
Author(s):  
Yi-xin Hao ◽  
Qiang Fu ◽  
Yan-Yan Guo ◽  
Ming Ye ◽  
Hui-Xia Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Kras Gene ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

scholarly journals Prognostic and Predictive Value of Circulating Tumor DNA in Patients with Advanced Colorectal Cancer and Chemotherapy

2021 ◽  
Author(s):  
Xiu Liu ◽  
Yibin Xie ◽  
Kai Ou ◽  
Xuan Zhang ◽  
Chelong Lu ◽  
...  
Keyword(s):  
Predictive Value ◽  
Residual Disease ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Copy Number Variations ◽  
Survival Times ◽  
Genetic Characteristics ◽  
Clinical Benefits ◽  
Patient Prognosis ◽  
Tumor Dna

Abstract Background: Advancedcolorectal cancer (CRC) remains a challenging disease requiring a multidisciplinary approach, combining surgery with chemotherapy, yet most cases still has worse outcomes. Molecular variations were considered to be related to the clinical response. Moreover, emerging data suggest that circulating tumor DNA (ctDNA) may detect minimal residual disease (MRD) and reflect treatment efficacyacross diverse cancer types. However, most reported ctDNA measurements are based on monitoring a few hotspot mutations and their predictive value in advanced CRCs are still undetermined. Here, we carried out WES sequencing to explore the genomic landscape in CRC patients and developedctDNA fingerprints panelswhich are based on the top somatic mutated genes of each individual to evaluate the early changes of ctDNA fingerprints in chemo-treated advanced CRC patients as a marker of clinical benefits.Methods: We enrolled 122 patients with CRC and analyzed their genetic profilinginclude somatic alterations and copy number variations. Meanwhile, we monitored their ctDNA fingerprints changes along the course of treatment by serial sampling of peripheral blood. Seventy-one of the patients were treated with standard chemotherapy, and theirctDNAfingerprints variations were used to assess the prognosis. We analyzed the correlation between ctDNA fingerprints levels and overall survival (OS) of the patients.Results: Among the 122 enrolled patients,theTP53 (70%), APC (59%) and KRAS (38%) are most frequently mutationsin CRC patients. The AHNAK mutation and HOXB-AS1 amplification are associated with survival times.We monitored the baseline ctDNAvalue and found thatthe ctDNA-high group has a shorter OS than that of the ctDNA-low group (HR, 2.89; CI 95% 1.45-5.79; p = 0.0027). The conclusion stands when only 48of the 122 patients, who had advanced CRC (stage IV) received chemotherapy (HR, 1.60; CI 95% 0.61-4.17; p = 0.037). Moreover, change of ctDNA fingerprints were associated with survival timesduring the course of chemotherapy, a decreased group has a favorable clinical benefit. We compared the performance of ctDNA fingerprints in predicting clinical outcomes with that of imaging-based diagnosis in 34 advanced CRC patients, andfound that 52.9% (18/34) of the patients had consistent outcomes between ctDNA fingerprints and imaging diagnosis.Conclusions: This study analysis the genetic characteristics of CRC patients and explore molecular markers related to the prognosis. It is also confirming the association between baseline levels of ctDNA fingerprints and survival times in CRCs. More importantly, it suggests early change of ctDNA fingerprints level in plasma is a promising biomarker of chemotherapy efficacy and patient prognosis in advanced CRCs.

scholarly journals Circulating Tumor DNA Allows Early Treatment Monitoring in BRAF- and NRAS-Mutant Malignant Melanoma

2020 ◽  
pp. 20-31 ◽  
Author(s):  
Jan Braune ◽  
Laura Keller ◽  
Florian Schiller ◽  
Erika Graf ◽  
David Rafei-Shamsabadi ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Stage Iii ◽  
Response To Treatment ◽  
Serum Samples ◽  
Free Survival ◽  
Tumor Dna ◽  
Stage Iv Melanoma

PURPOSE We evaluated circulating tumor DNA (ctDNA) for detecting tumor burden in melanoma and examined whether early changes in the number of ctDNA copies predict response to treatment. PATIENTS AND METHODS We included 12 patients with stage III and 50 patients with stage IV melanoma with BRAF exon 15 or NRAS exon 3 mutations in tumor tissue. We used droplet digital polymerase chain reaction to retrospectively analyze serial plasma samples for mutation-positive ctDNA. RESULTS Matched plasma and serum samples were positive for ctDNA, lactate dehydrogenase, and S100 in 113 (45.8%), 108 (43.7%; not significant), and 58 (23.5%; P < .0001) of 247 samples from 50 patients with stage IV melanoma, and in 17 (63%), eight (29.6%; P = .014), and five (18.5%; P < .0001) of 27 samples from 12 patients with stage III melanoma. The number of mutant ctDNA copies correlated with concentrations of lactate dehydrogenase ( r = 0.50) and S100 ( r = 0.64), tumor volume ( r2 = 0.58), and tumor metabolic activity ( r2 = 0.83). Within 30 days before surgery, initiation of treatment, or change in treatment, ctDNA, LDH, and S100 were positive in 76.8%, 53.6% ( P = .01), and 46.4% ( P < .001) of patients, respectively. In patients with stage III or IV melanoma, early changes in ctDNA within 1 month after initiation of treatment correctly predicted RECIST response categories in 19 of 20 patients. Detectable ctDNA within 30 days after surgery or initiation of systemic treatment predicted inferior progression-free survival in patients with stage III disease ( P = .018). In patients with stage IV disease, 10 or more copies of ctDNA per mL at first follow-up indicated shorter progression-free survival (3.8 v 9 months; hazard ratio, 4.05; 95% CI, 1.56 to 10.53). CONCLUSION ctDNA indicated active tumor and was an adverse prognostic marker for tumor progression. Dynamic changes in ctDNA allowed prediction of response early after initiation of treatment. These data support the use of ctDNA to guide treatment in melanoma.

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

scholarly journals Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1331
Author(s):  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Susie Brousse ◽  
Olga Savichtcheva ◽  
Kimberly A. Holden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genomic Instability ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
T1 And T2 ◽  
Tumor Dna

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). Methods: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). Results: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. Conclusions: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

scholarly journals Electroanalytical Biosensors for Circulating Tumor DNA Detection—A Brief Review

2021 ◽  
Author(s):  
Zhijia Peng ◽  
Xiaogang Lin ◽  
Weiqi Nian ◽  
Xiaodong Zheng ◽  
Jayne Wu
Keyword(s):  
Real Time ◽  
Point Of Care ◽  
Low Cost ◽  
High Sensitivity ◽  
High Specificity ◽  
Circulating Tumor Dna ◽  
Minimal Invasive ◽  
Diagnosis And Treatment ◽  
Detection Technology ◽  
Tumor Dna

Early diagnosis and treatment have always been highly desired in the fight against cancer, and detection of circulating tumor DNA (ctDNA) has recently been touted as highly promising for early cancer screening. Consequently, the detection of ctDNA in liquid biopsy gains much attention in the field of tumor diagnosis and treatment, which has also attracted research interest from the industry. However, traditional gene detection technology is difficult to achieve low cost, real-time and portable measurement of ctDNA. Electroanalytical biosensors have many unique advantages such as high sensitivity, high specificity, low cost and good portability. Therefore, this review aims to discuss the latest development of biosensors for minimal-invasive, rapid, and real-time ctDNA detection. Various ctDNA sensors are reviewed with respect to their choices of receptor probes, detection strategies and figures of merit. Aiming at the portable, real-time and non-destructive characteristics of biosensors, we analyze their development in the Internet of Things, point-of-care testing, big data and big health.

scholarly journals A Comparative Analysis of Tumors and Plasma Circulating Tumor DNA in 145 Advanced Cancer Patients Annotated by 3 Core Cellular Processes

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 701
Author(s):  
Kristian Larson ◽  
Radhamani Kannaiyan ◽  
Ritu Pandey ◽  
Yuliang Chen ◽  
Hani M. Babiker ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Cancer Patients ◽  
Cell Fate ◽  
Advanced Cancer ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Advanced Cancer Patients ◽  
Cellular Processes ◽  
Tumor Dna

Matched-targeted and immune checkpoint therapies have improved survival in cancer patients, but tumor heterogeneity contributes to drug resistance. Our study categorized gene mutations from next generation sequencing (NGS) into three core processes. This annotation helps decipher complex biologic interactions to guide therapy. We collected NGS data on 145 patients who have failed standard therapy (2016 to 2018). One hundred and forty two patients had data for tissue (Caris MI/X) and plasma cell-free circulating tumor DNA (Guardant360) platforms. The mutated genes were categorized into cell fate (CF), cell survival (CS), and genome maintenance (GM). Comparative analysis was performed for concordance and discordance, unclassified mutations, trends in TP53 alterations, and PD-L1 expression. Two gene mutation maps were generated to compare each NGS platform. Mutated genes predominantly matched to CS with concordance between Guardant360 (64.4%) and Caris (51.5%). TP53 alterations comprised a significant proportion of the mutation pool in Caris and Guardant360, 14.7% and 13.1%, respectively. Twenty-six potentially actionable gene alterations were detected from matching ctDNA to Caris unclassified alterations. The CS core cellular process was the most prevalent in our study population. Clinical trials are warranted to investigate biomarkers for the three core cellular processes in advanced cancer patients to define the next best therapies.

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