No abstract available.
CpG Islands* ; Methylation*

In forensic science practice, age is an important individual information, and one of the indicators to be considered first to depict features of the suspect. Recently, DNA methylation has become a research hotspot in age estimation because of its hig accuracy and stability. New progress has been made in specificity of DNA methylation sites, age estimation in multiple tissues, DNA methylation age estimation of minors, sensitivity of age estimation, forensic practical applications, etc. At the same time, several studies also established more accurate statistical modeling methods, eliminated differences between different detection platforms, found appropriate number of sites in models and analyzed the influence of environment and diseases. This review summarizes these to provide references.
CpG Islands ; DNA Methylation ; Forensic Genetics ; Humans

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.
Carcinogenesis ; CpG Islands ; Epigenomics ; Liver ; Melanoma* ; Methylation* ; Neoplasm Metastasis ; Phosphatidylinositols

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.
Carcinogenesis ; CpG Islands ; Epigenomics ; Liver ; Melanoma* ; Methylation* ; Neoplasm Metastasis ; Phosphatidylinositols

Colorectal cancer (CRC) has been assumed for many years to be a homogenous condition with the vast majority developing within preexisting-adenomas. However, over the last two-decades, it has become clear that CRC evolves through multiple pathways at the genetic and the epigenetic level. Each of these processes is associated with a unique genetic or epigenetic signature identifiable in the tumor cells. The pathway may be defined on the basis of three molecular features: 1) chromosomal instability (CIN), 2) microsatellite instability (MSI), and 3) CpG island methylator phenotype (CIMP). Those molecular pathways are determined at an early evolutionary stage and are fully established within early cancer. Recently, five subgroups were outlined by using morphological findings and associated molecular changes: type 1 (CIN-stable/ MSI-H/CIMP-H), type 2 (CIN-stable/MSI-L or MSS/ CIMP-H), type 3 (CIN-unstable/MSI-L or MSS/CIMP-L), type 4 (CIN-instable/MSS/CIMP-neg), and type 5 (CIN- stable/MSI-H/CIMP-neg). This approach to the classification of CRC should accelerate understanding of causation and will have an impact on clinical management in the areas of both prevention and treatment.
Chromosomal Instability ; Colorectal Neoplasms ; CpG Islands ; Epigenomics ; Microsatellite Instability ; Phenotype

CpG is the pair of nucleotides C and G, appearing successively, in this order, along one DNA strand. It is known that due to biochemical considerations CpG is relatively rare in most DNA sequences. However, in particular subsequences, which are a few hundred to a few thousand nucleotides long, the couple CpG is more frequent. These subsequences, called CpG islands, are known to appear in biologically more significant parts of the genome. The ability to identify CpG islands along a chromosome will therefore help us spot its more significant regions of interest, such as the promoters or 'start' regions of many genes. In this respect, I developed the CpG islands search tool, CpG Islands Detector, which was implemented in JAVA to be run on any platform. The window-based graphical user interface of CpG Islands Detector may facilitate the end user to employ this tool to pinpoint CpG islands in a genomic DNA sequence. In addition, this tool can be used to highlight potential genes in genomic sequences since CpG islands are very often found in the 5' regions of vertebrate genes.
Base Sequence ; CpG Islands ; DNA ; Genome ; Indonesia ; Nucleotides ; Vertebrates

With the improvement of DNA methylation detection techniques, studies on age-related methylation sites have found more age-specific ones across tissues, which improves the sensitivity and accuracy of age estimation. In addition, the establishment of various statistical models also provides a new direction for the age estimation of tissues from different sources. This review summarizes the related studies of age estimation based on DNA methylation from the aspects of detection technology, age-related cytosine phosphate guanine site and model selection in recent years.
DNA Methylation ; Forensic Genetics/methods* ; CpG Islands ; Forensic Medicine

PURPOSE: Promoter methylation is an important mechanism for silencing tumor-suppressor genes in cancer and it is a promising tool for the development of molecular biomarkers. The purpose of the present study was to investigate whether inactivation of the A Kinase Anchoring Protein 12 (AKAP12) gene is associated with promoter methylation in lung cancer. MATERIALS AND METHODS: The AKAP12 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) in ten lung cancer cell lines. The methylation status of the AKAP12alpha promoter was analyzed by performing bisulfite sequencing analysis in ten lung cancer cell lines, twenty four lung tissues and matched normal tissues. RESULTS: The AKAP12alpha expression was reduced in 6 of 10 (60%) lung cancer cell lines, whereas the AKAP12beta expression was absent in 1 of 10 (10%) lung cancer cell lines. The AKAP12alpha expression was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine in three lung cancer cell lines. Methylation of CpG island 1 in the AKAP12alpha promoter was detected in 30% of the lung cancer cell lines, whereas methylation of CpG island 2 in the AKAP12alpha promoter was observed in the immortalized bronchial cell line and in all the lung cancer cell lines. In lung tumors, the CpG island 1 in the AKAP12alpha promoter was infrequently methylated. However, CpG island 2 in the AKAP12alpha promoter was highly methylated in lung tumors compared with the surrounding normal tissues, and this was statistically significant (p=0.0001). CONCLUSION: Our results suggest that inactivation of the AKAP12alpha expression is associated with DNA methylation of the promoter region in lung cancer, and that AKAP12alpha may play an important role in lung cancer carcinogenesis.
Biomarkers ; Carcinogenesis ; Cell Line ; CpG Islands ; DNA Methylation ; Lung Neoplasms* ; Lung* ; Methylation* ; Phosphotransferases ; Promoter Regions, Genetic

PURPOSE: The loss of p16 protein has been frequently detected in breast carcinoma, but genetic alterations are infrequent. CpG islands of methylation within the p16 promotor have been identified as a mechanism that inactivates the p16 expression. The object of this study is to investigate the relationship between the loss of p16 protein and methylation as a molecular mechanism of the p16 gene inactivation in mammary tumorigenesis. METHODS : We performed an immunohistochemical assay of p16 protein in 70 cases of mammary carcinomas, and we tested for DNA methylation of p16 using methylation-specific PCR, and we then analyzed its correlation with the histopathologic variables. RESULTS : Among the 70 cases, the p16 expression was lost in 32 cases (45.7%), which was not significantly correlated with the pathologic variables. Twenty-three cases with and 27 cases without loss of p16 expression were tested for DNA methylation of p16. Twenty-one of the 23 interpretable cases with loss of p16 expression (91%) showed hypermethylation on p16, but there was no hypermethylation in any of the cases that were without the loss of the p16 expression. CONCLUSION: These findings suggest that the loss of the p16 expression is one of the common abnormalities observed in breast carcinoma and that methylation on the 5'CpG island of the p16 promoter is a major process for p16 ink4 inactivation in breast carcinoma.
Breast Neoplasms* ; Breast* ; Carcinogenesis ; CpG Islands ; DNA Methylation ; Genes, p16 ; Methylation ; Polymerase Chain Reaction

Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found. Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.
Carcinogens ; CpG Islands ; DNA Methylation ; Epigenomics ; Epithelial Cells ; Helicobacter pylori ; Herpesvirus 4, Human ; Humans ; Stomach Neoplasms