scholarly journals ThE uSE of AbErrAnT METhylATEd gEnES SEPT9 And VIM for clInIcAl dIAgnoSIS of colorEcTAl cAncEr

2016 ◽  
Vol 7 (4) ◽  
pp. 15-20
Author(s):  
O I Brovkina ◽  
M G Gordiev ◽  
D S Khodyrev ◽  
A G Nikitin ◽  
A V Averyanov
Keyword(s):  
Colorectal Cancer ◽  
High Sensitivity ◽  
Test System ◽  
Aberrant Methylation ◽  
Adjacent Tissue ◽  
Epigenetic Events ◽  
Combined Use ◽  
Ras Family ◽  
Definition Of ◽  
Tumor Dna

Definition of epigenetic disorders is important for early diagnosis of colorectal cancer. To obtain a model of diagnostic test system with high sensitivity and specificity, we determined the frequency of methylation in SEPT9 and VIM genes. Epigenetic events also were compared with mutations in the RAS family genes. It was confirmed the presence of aberrant methylation in SEPT9 and VIM genes in tumor cells. DNA of tumor samples was significantly more methylated than samples with DNA from adjacent tissue (P = 8,67E-19 for SEPT9 gene and P=8,68E-19 for VIM gene). In the group of patients carried mutations in KRAS or NRAS genes tumor DNA significantly more methylated in gene SEPT9 (P = 0.0018), in contrast to the tumor DNA from patients not carried mutations. We have demonstrated that the combined use of methylation markers can improve the sensitivity of the test systems used in the diagnostics of colon cancer.

scholarly journals THE ROLE OF ABERRANT METHYLATED IN GENES APC, RASSF1A AND ITGA4 FOR DIAGNOSIS OF COLORECTAL CANCER

2017 ◽  
Vol 8 (4) ◽  
pp. 8-14
Author(s):  
O I Brovkina ◽  
M G Gordiev ◽  
A N Toropovskiy ◽  
D S Khodyrev ◽  
Au Vyacheslavovich Nikitin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Diagnostic Test ◽  
Large Scale ◽  
High Reliability ◽  
Rectal Adenocarcinoma ◽  
Test System ◽  
Aberrant Methylation ◽  
Tissue Samples ◽  
Ras Family ◽  
The Republic

The “gold standard” of diagnosis of colorectal cancer (CRC) is a colonoscopy. Despite the high reliability, this method is not applicable in large-scale population screening or in estimation of the disease dynamics in a particular patient. In this study, we conducted an investigation of aberrant methylation in the APC, RASSF1A and ITGA4 genes. The study included 150 pairs of tumor tissue samples with known mutation status of the RAS family genes and the surrounding histologically unchanged tissue of patients with rectal adenocarcinoma treated at the Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan. The methylation profiles were studied using MethyLight PCR. The most difference in the methylation between tumor and healthy tissue was observed for the ITGA4 gene (sensitivity 78%, specificity 92.7%). For the APC gene sensitivity was 32%, specificity -93.3%, for the RASSF1 gene sensitivity was 85.3%, specificity - 56.7%. Previous data on the aberrant methylation of the SEPT9 and VIM genes and new data on the APC, RASSF1A and ITGA4 genes were compared with the mutations status in the KRAS and NRAS genes. The DNA of tumor samples was significantly more often methylated in the SEPT9 (P= 0.0018) and ITGA4 (P = 0.0044) genes in the group of patients carrying mutations in the KRAS or NRAS genes, in contrast to the DNA of tumor samples of non-carriers. In statistical analysis of the effectiveness of the diagnostic test system, it was shown that our model, which includes five methylation markers (APC, RASSF1A, ITGA4, SEPT9 and VIM), has the best sensitivity and specificity (82.7% and 97.3%, respectively). The obtained model of the diagnostic test system is proposed to be used for diagnostic problems.

scholarly journals Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform

Oncotarget ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 2549-2561 ◽  
Author(s):  
Evelyn Kidess ◽  
Kyra Heirich ◽  
Matthew Wiggin ◽  
Valentina Vysotskaia ◽  
Brendan C. Visser ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Tissue ◽  
Mutation Detection ◽  
High Sensitivity ◽  
Colorectal Cancer Patients ◽  
Tumor Dna ◽  
Mutation Profiling

scholarly journals Sensitive Quantification of Cell-Free Tumor DNA for Early Detection of Recurrence in Colorectal Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Sebastian Stasik ◽  
Marika Mende ◽  
Caroline Schuster ◽  
Sandra Mahler ◽  
Daniela Aust ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Cell ◽  
High Sensitivity ◽  
Disease Recurrence ◽  
Error Rates ◽  
Clinical Samples ◽  
Blood Collection ◽  
Clinical Routine ◽  
The Stability ◽  
Tumor Dna

The detection of plasma cell–free tumor DNA (ctDNA) is prognostic in colorectal cancer (CRC) and has potential for early prediction of disease recurrence. In clinical routine, ctDNA-based diagnostics are limited by the low concentration of ctDNA and error rates of standard next-generation sequencing (NGS) approaches. We evaluated the potential to increase the stability and yield of plasma cell–free DNA (cfDNA) for routine diagnostic purposes using different blood collection tubes and various manual or automated cfDNA extraction protocols. Sensitivity for low-level ctDNA was measured in KRAS-mutant cfDNA using an error-reduced NGS procedure. To test the applicability of rapid evaluation of ctDNA persistence in clinical routine, we prospectively analyzed postoperative samples of 67 CRC (stage II) patients. ctDNA detection was linear between 0.0045 and 45%, with high sensitivity (94%) and specificity (100%) for mutations at 0.1% VAF. The stability and yield of cfDNA were superior when using Streck BCT tubes and a protocol by Zymo Research. Sensitivity for ctDNA increased 1.5-fold by the integration of variant reads from triplicate PCRs and with PCR template concentration. In clinical samples, ctDNA persistence was found in ∼9% of samples, drawn 2 weeks after surgery. Moreover, in a retrospective analysis of 14 CRC patients with relapse during adjuvant therapy, we successfully detected ctDNA (median 0.38% VAF; range 0.18–5.04% VAF) in 92.85% of patients significantly prior (median 112 days) to imaging-based surveillance. Using optimized pre-analytical conditions, the detection of postoperative ctDNA is feasible with excellent sensitivity and allows the prediction of CRC recurrence in routine oncology testing.

scholarly journals Clinical Interest of the Combined Use of Serum CD26 and Alpha-L-Fucosidase in the Early Diagnosis of Colorectal Cancer

2004 ◽  
Vol 19 (6) ◽  
pp. 267-272 ◽  
Author(s):  
Daniel Ayude ◽  
María Páez de la Cadena ◽  
Oscar Javier Cordero ◽  
Montserrat Nogueira ◽  
José Ayude ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Diagnosis ◽  
Cancer Patients ◽  
High Sensitivity ◽  
High Specificity ◽  
The Other ◽  
Stage I ◽  
Combined Use ◽  
Clinical Interest ◽  
Colorectal Cancer Patients

The purpose of this study was to assess if the combination of CD26 and alpha-L-fucosidase has a role in the diagnosis of colorectal cancer, paying particular attention to the stages in which the tumour is not yet disseminated. CD26 concentration and alpha-L-fucosidase activity were determined in sera from 110 colorectal cancer patients and 46 donors. The combination of CD26 and alpha-L-fucosidase showed a specificity of 100% with a sensitivity of 64% in the diagnosis of colorectal cancer. Interestingly, the combination of both markers had a sensitivity of 75% in the stage I at the highest specificity (100%), providing also high sensitivity levels for the other non-disseminated stages (66% for stages II and III). In conclusion, the combined use of CD26 and alpha-L-fucosidase offers high sensitivity with high specificity in the diagnosis of colorectal cancer, especially at the earliest stage (TNM I).

Detector-C: A Blood-based IVD with High Sensitivity and Specificity for Early Detection and Screening of Colorectal Cancer

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
A Rosenthal ◽  
H Köppen ◽  
R Musikowski ◽  
R Schwanitz ◽  
J Behrendt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Sensitivity And Specificity ◽  
High Sensitivity

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 BIOM-62 SENSITIVE DETECTION AND DISCRIMINATION OF INTRACRANIAL TUMORS BY BLOOD

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii15-ii15
Author(s):  
Farshad Nassiri ◽  
Ankur Chakravarthy ◽  
Shengrui Feng ◽  
Roxana Shen ◽  
Romina Nejad ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Tumors ◽  
Model Performance ◽  
High Sensitivity ◽  
Circulating Tumor Dna ◽  
Low Grade ◽  
Learning Approaches ◽  
Intracranial Tumors ◽  
Cell Of Origin ◽  
Tumor Dna

Abstract BACKGROUND The diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Non-invasive diagnostic approaches, particularly for patients with brain tumours, provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. We reasoned that DNA methylation profiles of circulating tumor DNA in blood can be used as a clinically useful biomarker for patients with brain tumors, given the specificity of DNA methylation profiles for cell-of-origin. METHODS We generated methylation profiles on the plasma of 608 patients with cancer (219 intracranial, 388 extracranial) and 60 healthy controls using a cell-free methylated DNA immunoprecipitation combined with deep sequencing (cfMeDIP-seq) approach. Using machine-learning approaches we generated and evaluated models to distinguish brain tumors from extracranial cancers that may metastasize to the brain, as well as additional models to discriminate common brain tumors included in the differential diagnosis of solitary extra-axial and intra-axial tumors. RESULTS We observed high sensitivity and discriminative capacity for our models to distinguish gliomas from other cancerous and healthy patients (AUC=0.99, 95%CI 0.96–1), with similar performance in IDH mutant and wildtype gliomas as well as in lower- and high-grade gliomas. Excluding non-malignant contributors to plasma methylation did not change model performance (AUC=0.982, 95%CI 0.93–1). Models generated to discriminate intracranial tumors from each other also demonstrated high accuracy for common extra-axial tumors (AUCmeningioma=0.89, 95%CI 0.80–0.97; AUChemangiopericytoma=0.95, 95%CI 0.73–1) as well as intra-axial tumors ranging from low-grade indolent glial-neuronal tumors (AUC 0.93, 95%CI 0.80 – 1) to diffuse intra-axial gliomas with distinct molecular composition (AUCIDH-mutant glioma = 0.82, 95%CI 0.66 -0.98; AUCIDH-wildtype-glioma = 0.71, 95%CI 0.53 – 0.9). Plasma cfMeDIP-seq signals originated from corresponding tumor tissue DNA methylation signals (r=0.37, p< 2.2e-16). CONCLUSIONS These results demonstrate the potential for cfMeDIP-seq profiles to not only detect circulating tumor DNA, but to accurately discriminate common intracranial tumors that share cell-of-origin lineages.

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