Juergen Distler

T2026 Circulating Methylated Septin 9 DNA in Plasma Is a Biomarker for Colorectal Cancer

Introduction: The low sensitivity of the fecal occult blood tests (FOBT) based on the guaiac have made to develop new immunochemical tests with an efficiency to detect advanced neoplasia (advanced adenoma and colorectal cancer) still not well established. Aim: Determine the sensitivity and specificity of a FOBT based on the guaiac (FOBTg) with a quantitative immunochemical FOBT (FOBTi) to detect advanced neoplasia. Material and methods: Patients: all individuals with a colonoscopy programmed by any cause (screening, surveillance or symptoms) were included. Individuals with personal history of inflammatory bowel diseases or colorectal cancer were excluded. During the days previous to the exploration three high sensitivity FOBTg and two FOBTi (positive test ≥100ng/ml) were completed. The sample was calculated for demonstrating the superiority of the FOBTi of 15% of sensitivity with a final sample of 700 individuals. Results We presented the results of the first 140 individuals. The colonoscopy was performed for symptoms in 66% of cases and for screening or surveillance in 34% of cases. The colonoscopy detected 16 individuals (11%) with an advanced neoplasia (2 infiltrant carcinoma and 14 advanced adenomes). Other finds were: 20 patients with non advanced adenomes, 11 with polyps not adenomatous and 4 inflammatory colitis. The colonoscopy was normal in 88 (63%) individuals. The percentage of positive test was from 3,5% (5/140) and 16,5% (23/140) for the FOBTg and FOBTi, respectively. The sensitivity, specificity, positive predictive value and negative predictive value to detect an advanced neoplasia were 12%, 97%, 40% and 89% with the FOBTg and of 62,5%, 89%, 60,8%, 81% for the FOBTi. If considered only the first immunochemical test, the sensitivity, specificity, positive predictive value and negative predictive value were 43,7%, 92,7%, 43,7%, 92,7%, respectively. Conclusion The FOBTi is very superior to the FOBTg to detect advanced neoplasia although the high number of false positives could limit its use. The utilization of one or two FOBTi should be appraised depending on the disposable endoscopic resources.

DNA Methylation Analysis: Providing New Insight into Human Disease

Publisher Summary The human genome contains four bases—guanine, adenine, thymine, and cytosine. The cytosines can be either methylated or unmethylated at the fifth carbon position in the pyrimidine ring. In general, they can only be methylated when they are in the context of a CpG dinucleotide that involves a cytosine immediately followed by a guanine. The methylation status of a CpG island is correlated with the chromatin structure and expression levels of nearby genes. CpG islands associated with actively transcribed genes are typically unmethylated. When a CpG island is methylated, methyl-CpG-binding domain proteins recognize the methylated CpG and recruit the necessary factors for chromatin condensation and gene inactivation. This DNA methylation state is maintained during cell division by a family of enzymes called DNA methyltransferases. Cancer was viewed as an accumulation of chromosomal aberrations and, therefore, called a “genetic disease.” However, it has become clear over time that epigenetic changes play a crucial role in carcinogenesis. While attention is focused on methylation in carcinogenesis, a similar groundswell of research is emerging on methylation in other diseases, especially autoimmune and cardiovascular conditions.

DNA Methylation Analysis

Publisher Summary The human genome contains four bases—guanine, adenine, thymine, and cytosine. The cytosines can be either methylated or unmethylated at the fifth carbon position in the pyrimidine ring. In general, they can only be methylated when they are in the context of a CpG dinucleotide that involves a cytosine immediately followed by a guanine. The methylation status of a CpG island is correlated with the chromatin structure and expression levels of nearby genes. CpG islands associated with actively transcribed genes are typically unmethylated. When a CpG island is methylated, methyl-CpG-binding domain proteins recognize the methylated CpG and recruit the necessary factors for chromatin condensation and gene inactivation. This DNA methylation state is maintained during cell division by a family of enzymes called DNA methyltransferases. Cancer was viewed as an accumulation of chromosomal aberrations and, therefore, called a “genetic disease.” However, it has become clear over time that epigenetic changes play a crucial role in carcinogenesis. While attention is focused on methylation in carcinogenesis, a similar groundswell of research is emerging on methylation in other diseases, especially autoimmune and cardiovascular conditions.

Chapter 6 – DNA Methylation Analysis: Providing New Insight into Human Disease

Publisher Summary The human genome contains four bases—guanine, adenine, thymine, and cytosine. The cytosines can be either methylated or unmethylated at the fifth carbon position in the pyrimidine ring. In general, they can only be methylated when they are in the context of a CpG dinucleotide that involves a cytosine immediately followed by a guanine. The methylation status of a CpG island is correlated with the chromatin structure and expression levels of nearby genes. CpG islands associated with actively transcribed genes are typically unmethylated. When a CpG island is methylated, methyl-CpG-binding domain proteins recognize the methylated CpG and recruit the necessary factors for chromatin condensation and gene inactivation. This DNA methylation state is maintained during cell division by a family of enzymes called DNA methyltransferases. Cancer was viewed as an accumulation of chromosomal aberrations and, therefore, called a “genetic disease.” However, it has become clear over time that epigenetic changes play a crucial role in carcinogenesis. While attention is focused on methylation in carcinogenesis, a similar groundswell of research is emerging on methylation in other diseases, especially autoimmune and cardiovascular conditions.