scholarly journals The mutational landscape of gastrointestinal malignancies as reflected by circulating tumor DNA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11574-11574
Author(s):  
Paul Riviere ◽  
Paul T. Fanta ◽  
Sadakatsu Ikeda ◽  
Joel Micah Baumgartner ◽  
Gregory M. Heestand ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Treatment Options ◽  
Circulating Tumor Dna ◽  
Genetic Alterations ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Malignancies ◽  
Appendiceal Adenocarcinoma ◽  
Cancer Types ◽  
Tumor Dna

11574 Background: Liquid biopsy of circulating tumor DNA (ctDNA) is a novel method of detecting genetic alterations in cancer patients without tissue acquisition. Methods: Our analysis surveyed the genomic landscape of 213 patients with various gastrointestinal malignancies using next generation sequencing of plasma ctDNA across a 68 gene panel (www.guardanthealth.com/guardant360/). Data analysis was performed following UCSD IRB guidelines for de-identified database (NCT02478931). Results: The most common cancer types were colorectal adenocarcinoma (N = 55 (26%)), appendiceal adenocarcinoma (N = 46 (22%)), hepatocellular carcinoma (N = 31 (15%)), and pancreatic ductal adenocarcinoma (N = 25 (12%)). 70% of patients had discernible alteration(s), and 58% of patients had ≥1 characterized alterations. The median number of characterized alterations per patient was 1 (range 0-13). The number of detected alterations per patient varied between cancer types: in hepatocellular carcinoma, 74% of patients (23/31) had > 1 characterized alteration(s), whereas 76% of patients (35/46) with appendiceal adenocarcinoma had no characterized alterations. Overall, of 123 patients with characterized alterations, > 99% (122/123) had ≥1 hypothetical (experimental or approved) treatment options available. Potentially targetable alterations varied between cancer types, proportionally to the detection rate of characterized alterations. The median percent ctDNA of characterized alterations was 2.50% (IQR 0.76-8.96%). Of interest, 95% of patients (117/123) had distinct molecular portfolios. Altogether, there were 143 unique characterized alterations within 56 genes. Overall concordance rates of 96%, 94%, 95%, and 91%, respectively, were found between ctDNA and tissue biopsy (105 patients) (https://www.foundationmedicine.com/) in the four most common alterations ( KRAS amplification, MYC amplification, KRAS G12V, and EGFR amplification). Conclusions: Our observations suggest that many patients with gastrointestinal tumors have discernible and pharmacologically tractable ctDNA alterations. Hence, ctDNA assessment through non-invasive liquid biopsy may have an important role in clinical practice.

Monitoring treatment efficacy and resistance in breast cancer patients via circulating tumor DNA genomic profiling.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12502-e12502
Author(s):  
Wang Xiao Jia ◽  
Zhan-Hong Chen ◽  
Tian Sun ◽  
Zi Yan Yang ◽  
Yabing Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Somatic Mutations ◽  
Target Therapy ◽  
Chemotherapy Resistance ◽  
Circulating Tumor Dna ◽  
Genetic Alterations ◽  
Longitudinal Analyses ◽  
Trastuzumab Resistance ◽  
Tumor Dna

e12502 Background: Circulating tumor DNA (ctDNA) from liquid biopsy provides a valuable assessment of invasive breast cancer (BC). We evaluated the utility of ctDNA to reflect the efficacy of HER2-targeted trastuzumab in treating HER2+ BC patients, as well as chemotherapy in treating HER2- BC patients, to monitor trastuzumab and chemotherapy resistance mechanisms. Methods: Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed in 41 plasma biopsy samples from 19 HER2+ and 12 HER2- BC patients in a retrospective study. We compared ctDNA somatic mutations and germline mutations for analyzing acquired and innate resistance, respectively. Results: ERBB2 somatic copy number of HER2+ BC patients who developed progressed diseases to HER2-target therapy was significantly higher than those benefited from HER2-target therapy. HER2+ BC patients who developed acquired resistance to trastuzumab showed frequent genomic alterations on ERBB2, TP53, EGFR, NF1 and SETD2 genes. Specifically, in longitudinal analyses, somatic mutations found in the original breast tumor can be detected in the liver metastasis and plasma ctDNA with increased allele frequencies. Newly emerged deleterious mutations occurred when the patient was benefiting from trastuzumab, predicting the poor prognosis. From these newly emerged somatic mutations, EBBB2L869R was further investigated in vitro and contributed to trastuzumab resistance. In the HER2- BC patients with chemotherapy resistance, frequently genetic alterations on TP53, PIK3CA and DNA damage repair genes were observed in ctDNA mutation profiling. Conclusions: liquid biopsy ctDNA, particularly longitudinal analyses, provides insights into targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2- BC patients, respectively.

scholarly journals Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers

2017 ◽  
Vol 114 (38) ◽  
pp. 10202-10207 ◽  
Author(s):  
Joshua D. Cohen ◽  
Ammar A. Javed ◽  
Christopher Thoburn ◽  
Fay Wong ◽  
Jeanne Tie ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Control Cohort ◽  
Protein Biomarkers ◽  
Pancreatic Cancers ◽  
Single Marker ◽  
Diagnosis Of Cancer ◽  
Cancer Types ◽  
Tumor Dna

The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests forKRASgene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer.KRASmutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient’s primary tumor (100% concordance). The use ofKRASin conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.

scholarly journals Circulating Tumor DNA in Oncology

Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2198
Author(s):  
Saeko Sakaeda ◽  
Yoichi Naito
Keyword(s):  
Early Detection ◽  
Tumor Cells ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Genetic Alterations ◽  
Patients With Cancer ◽  
Health Consciousness ◽  
Number Of Patients ◽  
Diagnosis Of Cancer ◽  
Tumor Dna

When somatic cells in the human body undergo apoptosis or necrosis, the released DNA enters the bloodstream. This type of DNA is called cell-free DNA (cfDNA). In patients with cancer, DNA released from tumor cells is called circulating tumor DNA (ctDNA), which carries genetic alterations specific to tumor cells. In recent years, ctDNA has attracted particular attention in terms of the concept of liquid biopsy in cancer care. Conventionally, tissue biopsy is required for the definitive diagnosis of cancer, and imaging examinations, such as CT, are performed for evaluating recurrence and residual lesions. Although the treatment burden on cancer patients is being slightly reduced due to advances in medicine, invasive examinations and medical exposure are still unavoidable. In addition, the prognosis of cancer varies considerably depending on the degree of progression at the time of detection. Therefore, the early detection of cancer is of utmost importance. With the increase in health consciousness, more people undergo regular health checkups, and it becomes necessary to diagnose cancer in a larger number of patients at an earlier stage. Although the accuracy of early detection has been improved by new imaging tests and examination techniques, each organ must be examined separately, and some organs are more difficult to examine than others in a regular health checkup. The process of cancer screening, diagnosis, and detection of recurrence after treatment is extensive. It can also be expensive, and some of the examinations may be invasive. If all of these processes can be replaced by the analysis of ctDNA in liquid biopsy, only a single blood sample is required. Under these circumstances, various studies are currently in progress on the use of ctDNA in clinical practice as an approach that may greatly reduce such burden. We present an overview of the current situation of ctDNA, as well as its future issues and prospects.

scholarly journals Experimental Models of Liquid Biopsy in Hepatocellular Carcinoma Reveal Clone‐Dependent Release of Circulating Tumor DNA

2021 ◽  
Author(s):  
Ismail Labgaa ◽  
Johann Felden ◽  
Amanda J. Craig ◽  
Sebastiao N. Martins‐Filho ◽  
Carlos Villacorta‐Martin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Experimental Models ◽  
Tumor Dna

scholarly journals Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gillian Vandekerkhove ◽  
Jean-Michel Lavoie ◽  
Matti Annala ◽  
Andrew J. Murtha ◽  
Nora Sundahl ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Treatment Options ◽  
Circulating Tumor Dna ◽  
Molecular Stratification ◽  
Clinical Biomarkers ◽  
Surgery Patient ◽  
Metastatic Urothelial Carcinoma ◽  
Ctdna Analysis ◽  
Clinical Genomic ◽  
Tumor Dna

AbstractMolecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.

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