Masterarbeit, 2010
91 Seiten, Note: A
1 INTRODUCTION
2 REVIEW OF LITERATURE
a Anatomical consideration
b Physiology
c Tumors of the colon and rectum
3 MATERIALS AND METHODS
4 OBSERVATIONS AND RESULTS
5 DISCUSSION
6 SUMMARY AND CONCLUSION
7 BIBLIOGRAPHY
8 APPENDICES
I Certificate from The Chicago University
II Clinical proforma
III Preparation of stains and chemicals
IV Tissue processing and staining procedures
V Protocol for DNA extraction
VI Protocol for DNA methylation
VII TNM staging system
VIII Master table
IX Illustrations
The primary aim of this study is to examine the clinicopathologic patterns and epigenetic alterations, specifically DNA methylation, in colorectal carcinoma within a cohort of Bangladeshi patients, with the ultimate goal of identifying potential associations between molecular signatures and clinical outcomes.
2.3.3.3 DNA methylation in cancer
Cancer results from the accumulation of mutation in the genes. In addition to genetic mutation, this epigenetic change has been included as an alternative mechanism to cancer development. Epigenetics refers to change in the pattern of gene expression by mechanisms other than alterations in the primary nucleotide sequence of a gene(Herman, 2003). DNA methylation is the enzymatic attachment of methyl group to the 5th carbon of the cytosine base (Samarakoon, 2010). Methylation usually occurs in the CpG islands, a cytosine guanosine rich region in the DNA. In humans, DNA methylation is carried out by a group of enzymes called DNA methyltransferases. The letter “p” here signifies that the C and G are connected by a phosphodiester bond. Methylation patterns in tumor cells are significantly different from those in normal cells (Herman, 2003).
Silencing or inactivation of tumour suppressor gene is seen in cancers mostly due to hypermethylation. Hypermethylation profiling over more than 15 tumor types (colon, stomach, pancreas, liver, kidney, lung, breast, ovary, endometrium, kidney, bladder, brain, and leukemia and lymphomas) has shown that all the metabolic pathways are affected by promoter hypermethylation-associated silencing. Hypomethylation leads to the inappropriate and increased levels of gene expression in tumors such as oncogene activation (Samarakoon, 2010).
1 INTRODUCTION: Presents the global and regional epidemiology of colorectal cancer, emphasizing its rising incidence and the significance of epigenetic markers like DNA methylation.
2 REVIEW OF LITERATURE: Covers the anatomical, physiological, and pathological foundations of the colon, including tumor classification and current molecular understandings of colorectal carcinogenesis.
3 MATERIALS AND METHODS: Describes the study design, patient selection criteria, sample collection for histopathological and molecular analysis, and the laboratory techniques utilized.
4 OBSERVATIONS AND RESULTS: Provides a comprehensive data analysis regarding age, gender, clinical presentation, and specific DNA methylation findings in the studied patients.
5 DISCUSSION: Interprets the study results in the context of existing literature, discussing differences in age of onset and tumor characteristics in the Bangladeshi population.
6 SUMMARY AND CONCLUSION: Recapitulates the key findings of the study and offers concluding remarks on the role of DNA methylation in colorectal carcinoma pathogenesis.
Colorectal cancer, DNA methylation, Epigenetics, Adenocarcinoma, Tumor grade, TNM staging, Hypermethylation, Hypomethylation, Bangladeshi population, Histopathology, CpG islands, Molecular pathogenesis, Oncology, Clinical presentation, Prognostic factors.
This research focuses on investigating the clinicopathological features and DNA methylation patterns of colorectal carcinoma in a group of patients from Bangladesh.
The study revolves around colorectal cancer epidemiology, the molecular mechanism of DNA methylation in tumor development, histopathological tumor grading, and clinical staging.
The objective is to determine the morphologic pattern, clinical presentation, and specific DNA methylation changes in colorectal carcinoma tissues compared to corresponding normal colonic tissues.
The study utilized histopathological examination for tumor classification and grading, along with Infinium Assay technology to analyze genome-wide DNA methylation status in 24 paired tissue samples.
The main body covers a comprehensive review of existing colorectal cancer literature, the methodological approach to data collection and molecular processing, detailed observational results of patient cases, and an analytical discussion comparing these findings to global trends.
The most defining keywords include colorectal cancer, DNA methylation, epigenetics, histopathology, and Bangladeshi patient population.
DNA methylation, specifically hypermethylation, can lead to the silencing or inactivation of tumor suppressor genes, while hypomethylation can lead to the inappropriate activation of oncogenes, both of which drive neoplastic transformation.
The study observed that the average age at diagnosis in the studied Bangladeshi population is lower than that reported in many Western and other international studies.
The study analyzed several prognostic factors including tumor stage, histological grading, lymphovascular invasion, circumferential margin involvement, and the presence of tumor-infiltrating lymphocytes.
The tumor differential score helps quantify the significance of differences in methylation status between normal and tumor tissues, where positive values indicate hypermethylation and negative values indicate hypomethylation.
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