scholarly journals Molecular Alterations of Circulating Cell-Free DNA in the Pathological Progression of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Wenbo Guo ◽  
Jilin Lu ◽  
Linlin Yan ◽  
Debin Sun ◽  
Longlong Gong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Diagnosis ◽  
Gene Mutations ◽  
Gene Panel ◽  
Operating Characteristics ◽  
Cell Free Dna ◽  
Molecular Alterations ◽  
Free Dna ◽  
Mutation Burden ◽  
Early Hcc

Background. Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Early diagnosis of HCC is important to reduce the mortality rate. The aim of this study is to explore the plasma cell-free DNA (cfDNA) mutation profile in the pathological progression of HCC and to investigate the significance of plasma cfDNA mutations in the early diagnosis of HCC. Methods. Thirty-seven patients with chronic hepatitis B (CHB), eight with liver cirrhosis (LC), and eleven with HCC were enrolled in this cohort. Plasma cfDNA and white blood cell DNA were isolated, and plasma cfDNA mutation profiles were detected using a targeted gene panel. Results. The sequencing results of plasma cfDNA showed that HCC-related gene mutations were present in patients with CHB and LC. The mutation burden of HCC-related genes increased from CHB and LC to HCC. In patients with HCC, the average mutation burden of NRAS (10.1%), TP53 (7.4%), PTEN (4.2%), and APOB (2.6%) was the highest. The average mutation burden of PTEN, APOB, FRAS1, KDM6A, DDR2, TTK, NRAS, TP53, PTPRB, MPL, FCRL1, HN1, and SFN gradually increased from CHB and LC to HCC. The mutation burden of 18 HCC-related genes had an area under the receiver operating characteristics of 0.92 for the diagnosis of HCC. Conclusions. The mutation burden of HCC-related genes increased from CHB and LC to HCC. An optimal combination of cfDNA mutations in the gene panel for diagnosing HCC in patients with CHB and LC was selected. Our study indicates that somatic mutations in plasma cfDNA may serve as potential biomarkers for early HCC diagnosis.

scholarly journals Identification of Somatic Mutations in Papanicolaou Smear DNA and Plasma Circulating Cell-Free DNA for Detection of Endometrial and Epithelial Ovarian Cancers: A Pilot Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Xuan Jiang ◽  
Weihua Li ◽  
Jiaxin Yang ◽  
Shuzhen Wang ◽  
Dongyan Cao ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Somatic Mutations ◽  
Pap Smear ◽  
Hot Spot ◽  
Gene Mutations ◽  
Gene Panel ◽  
Pap Smears ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna

ObjectivesThe aim of this study was to identify tumor-derived DNA from Papanicolaou (Pap) smear and plasma specimens collected from patients with endometrial cancer or atypical hyperplasia (EC/AH) or epithelial ovarian cancer (OC).MethodsTumor tissues, peripheral blood, and Pap smear samples were collected from patients with EC/AH and patients with epithelial OC. Somatic mutations of tumor specimens in EC/AH and OC were examined by whole-exome sequencing using a 127-driver gene panel from The Cancer Genome Atlas (TCGA). A nine-gene EC/AH panel and an eight-gene OC panel were established based on the identified significantly mutated genes in the EC/AH and OC tumor specimens. Circulating single-molecule amplification and resequencing technology (cSMART) was applied to evaluate somatic mutations in Pap smear DNA and plasma circulating cell-free DNA (ccfDNA) using the EC/AH and OC gene panels.ResultsIn EC/AH group, there existed 22 tumors and 14 of the 22 tumors contributed hot spot mutations for the EC/AH nine-gene panel. In the Pap smear subgroup, all 21 Pap smears tested positive. Nine out of 11 (81.8%) identified the same gene mutations with their matched tumors and the remaining 10 Pap smears all tested positive. In the plasma subgroup, 10 out of 26 (38.5%) plasmas tested positive. One out of 13 (7.7%) identified the same gene mutation with its matched tumor and 5 out of the remaining 13 plasmas (38.5%) tested positive. In OC group, there existed 17 tumors and 16 of the 17 tumors contributed hot spot mutations for the OC eight-gene panel. In the Pap smear subgroup, all 11 Pap smears tested positive. Five out of 10 (50.0%) identified the same gene mutations with their matched tumors and the remaining one Pap smear also tested positive. In the plasma subgroup, all 22 plasmas tested positive. Ten out of 14 (71.4%) identified the same gene mutation with their matched tumors and the remaining 4 plasmas all tested positive.ConclusionsTumor-derived DNA can be detected in Pap smears and plasmas from patients with EC/AH or epithelial OC. Using a small gene-panel, early detection of EC/AH and OC might be promising. However, the value of plasma ccfDNA for EC/AH requires further investigation.

scholarly journals Value of Quantitative and Qualitative Analyses of Circulating Cell-Free DNA as Diagnostic Tools for Hepatocellular Carcinoma

Medicine ◽  
2015 ◽  
Vol 94 (14) ◽  
pp. e722 ◽  
Author(s):  
Wenjun Liao ◽  
Yilei Mao ◽  
Penglei Ge ◽  
Huayu Yang ◽  
Haifeng Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Diagnostic Tools ◽  
Cell Free Dna ◽  
Free Dna ◽  
Qualitative Analyses ◽  
Circulating Cell Free Dna

Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-Free DNA

JAMA Oncology ◽  
2021 ◽  
Author(s):  
Michael T. Schweizer ◽  
Smruthy Sivakumar ◽  
Hanna Tukachinsky ◽  
Ilsa Coleman ◽  
Navonil De Sarkar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Gene Mutations ◽  
Repair Gene ◽  
Cell Free Dna ◽  
Metastatic Tissue ◽  
Free Dna ◽  
Primary Prostate Cancer ◽  
Dna Repair Gene

scholarly journals Effectiveness of 12-13-week scan for early diagnosis of fetal congenital anomalies in the cell-free DNA era

2018 ◽  
Vol 51 (4) ◽  
pp. 463-469 ◽  
Author(s):  
M. J. A. Kenkhuis ◽  
M. Bakker ◽  
F. Bardi ◽  
F. Fontanella ◽  
M. K. Bakker ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Congenital Anomalies ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Preferred end coordinates and somatic variants as signatures of circulating tumor DNA associated with hepatocellular carcinoma

2018 ◽  
Vol 115 (46) ◽  
pp. E10925-E10933 ◽  
Author(s):  
Peiyong Jiang ◽  
Kun Sun ◽  
Yu K. Tong ◽  
Suk Hang Cheng ◽  
Timothy H. T. Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Peripheral Circulation ◽  
Sequence Information ◽  
Sequencing Analysis ◽  
Plasma Samples ◽  
Dna Molecules ◽  
Plasma Dna ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

Circulating tumor-derived cell-free DNA (ctDNA) analysis offers an attractive noninvasive means for detection and monitoring of cancers. Evidence for the presence of cancer is dependent on the ability to detect features in the peripheral circulation that are deemed as cancer-associated. We explored approaches to improve the chance of detecting the presence of cancer based on sequence information present on ctDNA molecules. We developed an approach to detect the total pool of somatic mutations. We then investigated if there existed a class of ctDNA signature in the form of preferred plasma DNA end coordinates. Cell-free DNA fragmentation is a nonrandom process. Using plasma samples obtained from liver transplant recipients, we showed that liver contributed cell-free DNA molecules ended more frequently at certain genomic coordinates than the nonliver-derived molecules. The abundance of plasma DNA molecules with these liver-associated ends correlated with the liver DNA fractions in the plasma samples. Studying the DNA end characteristics in plasma of patients with hepatocellular carcinoma and chronic hepatitis B, we showed that there were millions of tumor-associated plasma DNA end coordinates in the genome. Abundance of plasma DNA molecules with tumor-associated DNA ends correlated with the tumor DNA fractions even in plasma samples of hepatocellular carcinoma patients that were subjected to shallow-depth sequencing analysis. Plasma DNA end coordinates may therefore serve as hallmarks of ctDNA that could be sampled readily and, hence, may improve the cost-effectiveness of liquid biopsy assessment.

scholarly journals Cell-free DNA From Pleural Effusion Samples: Is It Right for Molecular Testing in Lung Adenocarcinoma?

2021 ◽  
Vol 27 ◽  
Author(s):  
Attila Mokánszki ◽  
Emese Sarolta Bádon ◽  
Anikó Mónus ◽  
László Tóth ◽  
Nóra Bittner ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Gene Mutations ◽  
Molecular Testing ◽  
Alternative Source ◽  
Cell Free Dna ◽  
Molecular Features ◽  
Free Dna ◽  
Mutational Status ◽  
Therapeutic Decisions

Pathogenic molecular features gained specific significance in therapeutic decisions in lung carcinoma in the past decade. Initial and follow up genetic testing requres appropriate amounts and quality of tumor derived DNA, but tumor sampling, especially for disease monitoring is generally limited. Further to the peripheral blood (PB), samples from pleural fluid, accumulating in diverse lung processes might serve as an alternative source for cell-free DNA (cfDNA) for genetic profiling. In our study, cfDNA isolated from the pleural effusion and from the PB, and genomic DNA (gDNA) obtained from tissue/cellular samples were analyzed and compared from altogether 65 patients with pulmonary disease, including 36 lung adenocarcinomas. The quantity of effusion cfDNA yield appeared to be significantly higher compared to that from simultaneously collected PB plasma (23.2 vs. 4.8 ng/μl, p < 0.05). Gene mutations could be safely demonstrated from the effusion cfDNA fraction obtained from adenocarcinoma patients, 3/36 EGFR, 9/36 KRAS and 1/36 BRAF gene variants were detected. In this series, 9/13 samples showed an effusion+/plasma-mutational status, while only 1/13 samples presented with the opposite findings (effusion-/plasma+). gDNA analysis from sediment cell blocks from the identical effusion sample was surprisingly ineffective for lung adenocarcinoma profiling due to the low DNA yield. In conclusion, the cell free supernatant of pleural effusions appears to concentrate cancer derived cfDNA and seems to be particularly suitable for serial genotyping of pulmonary adenocarcinoma.

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