The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ying Jieer - One of the best experts on this subject based on the ideXlab platform.
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detection of CDH1 Gene variants in early onset diffuse gastric cancer in chinese patients
Journal of Clinical Oncology, 2014Co-Authors: Ying JieerAbstract:e15079 Background: To study the correlation between the type and frequency of exon variants in E- cadherin (CDH1) Gene and clinical characteristics of early-onset diffuse gastric cancer (EODGC) in ...
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searching for CDH1 Gene mutations in early onset diffuse gastric cancer in chinese patients
Journal of Clinical Oncology, 2014Co-Authors: Xu Yanjun, Cao Wenming, Guo Jianmin, Wang Xinbao, Cheng Xiangdong, Ying JieerAbstract:23 Background: CDH1 germline mutations are found to be associated with the development of hereditary diffuse gastric cancer (HDGC) and the early-onset diffuse gastric cancer (EODGC). But the impact of CDH1 Gene mutations and large deletions on HDGC and EODGC has not been fully determined in Asians. Although the incidence of gastric cancer is relatively high in China, the detection rate of CDH1 germline mutations in Chinese patients with EODGC is rare compared to that in European patients. Methods: We investigated the mutation status of the CDH1 Gene in 57 Chinese EODGC patients younger than 40 years old who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. Associations between mutation, clinicopathologic, and overall survival data were analyzed by SPSS 19. Results: The germline mutations of CDH1Gene were identified in 51 (89.5%) of the...
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detection of CDH1 Gene variants in early onset diffuse gastric cancer in chinese patients
Clinical Laboratory, 2014Co-Authors: Xu Yanjun, Cao Wenming, Guo Jianmin, Wang Xinbao, Cheng Xiangdong, Ying Lisha, Ying JieerAbstract:BACKGROUND The type and frequency of E-cadherin (CDH1) germline variants in China for the early-onset diffuse gastric cancer (EODGC) has not been well established. Our study tend to screen and characterize germline variants for CDH1 Gene in EODGC patients and in General population in China. METHODS Peripheral blood samples were collected from 57 EODGC patients (age ≤ 40 years) who underwent resection surgery for primary gastric cancer. DNA was extracted from peripheral blood leucocytes and polymerase chain reaction amplification (PCR) was performed to amplify and sequence the CDH1 Gene. Statistical analysis was performed using the SPSS 19 software. RESULTS CDH1 Genetic screening results: 2 missense in exon 5 (c.778G > C, 26.3%) and 12 (c.2012C > G, 1.8%), and 1 synonymous (c.2200T > C, 72.8%) in exon 13. According to the c.2200T > C variant, the CDH1 C frequency was 62.3% and the T frequency 37.7%, while the CC homozygote frequency was 43.9%, the TT homozygote 19.3% and the CT heterozygote 36.8%. According to the c.778G > C variant, the CDH1 C frequency was 15.8% and the G frequency 84.2%, while the GG homozygote frequency was 68.4%, the GC heterozygote 31.6%. When comes to the c.2012C > G variant, the CDH1 C frequency was 98.2% and the G frequency 1.8%, while the CC homozygote frequency was 96.5%, the GC heterozygote 3.5%. Statistical association was analyzed among the EODGC patients and BDs group tested for the three variants. Lymph node metastasis rate was found to be significantly higher in patients with c.2200T > C (P = 0.04). The difference in OS with or without c.2200T > C variant was found to be sig- nificant (P < 0.05). CONCLUSIONS No deletions or insertions were found in the CDH1 exon boundaries. All of the variants resulted com- mon polymorphisms. CDH1 germline variants are present in EODGC patients in Chinese population, but they are mainly missense variants with unknown function which are likely associated with lymph node metastasis and OS.
Masahiko Shiraishi - One of the best experts on this subject based on the ideXlab platform.
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5 aza 2 deoxycytidine reactivates the CDH1 Gene without influencing methylation of the entire cpg island or histone modification in a human cancer cell line
Proceedings of the Japan Academy. Series B Physical and Biological Sciences, 2004Co-Authors: Ken Tachibana, Ken Takeda, Masahiko ShiraishiAbstract:It is well-recognized that DNA methylation and histone modifications play critical roles in epiGenetic regulation of Gene activity through the alteration of chromatin structure. Recent studies have shown that in a subset of cancer cells, the silencing of the human E-cadherin (CDH1) Gene is associated with hypermethylation of the CpG island. However, the associated molecular mechanism remains unclear. To understand the mechanism, we have investigated the alteration of CpG island methylation and histone modifications during the reactivation of the CDH1 Gene by treatment with 5-aza-2'-deoxycytidine (5-aza-dC). Although the CDH1 Gene expression was recovered by treatment with 5-aza-dC in a liver cancer cell line Li21, the methylation status of the entire CpG island and acetylation and methylation status of associated histones were not significantly altered. These results demonstrate that the silenced CDH1 Gene can be reactivated without apparent alteration of histone modification or CpG island methylation. (Communicated by Takashi SUGIMURA, M.J.A.)
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heteroGeneity in the modification and involvement of chromatin components of the cpg island of the silenced human CDH1 Gene in cancer cells
Nucleic Acids Research, 2002Co-Authors: Shiro Koizume, Ken Tachibana, Takao Sekiya, Setsuo Hirohashi, Masahiko ShiraishiAbstract:The structural alteration of chromatin has a key role in regulating Gene expression. The alteration of chromatin is mediated by modification of its components. Detailed understanding of the relationship between these modifications, notably, methylation of the full-length CpG island, the association of methyl-CpG binding proteins (MBPs), and the acetylation and methylation of histones in Gene silencing is vitally important. Currently, however, the manner in which chromatin components, associated with a specific Gene, are modified is poorly understood. Here we provide in vivo evidence in cancer cells of the differential association between CpG methylation, MBPs, and histone modification in the entire CpG island of the human E-cadherin (CDH1) Gene. Of the cell lines with CDH1 transcriptional repression, the distribution of methyl-CpGs in the CpG island differed markedly. In a cell line with Gene silencing, the promoter region was almost methylation-free. Chromatin immunoprecipitation analysis revealed that the acetylation status of histone H4 differed between cell lines. However, deacetylated histone H3 was associated with the CpG island in all silenced cell lines. Binding of MeCP2 was also detected in all silenced cell lines. Additional binding of MBD1 protein was detected in a cell line in which the promoter region was poorly methylated and only histone H3 was deacetylated. Binding of MBD2 protein was detected in all other silenced cell lines. Histone H3 lysine 9 was methylated in all silenced cells, while histone H3 lysine 4 was methylated in some silenced cell lines. These results demonstrate that chromatin components associated with inactive CDH1 chromatin is heteroGeneously modified and suggests the presence of multiple pathways for the formation of inactive chromatin.
Hidetaka Yamada - One of the best experts on this subject based on the ideXlab platform.
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early onset diffuse gastric cancer associated with a de novo large genomic deletion of CDH1 Gene
Gastric Cancer, 2014Co-Authors: Shinya Sugimoto, Hidetaka Yamada, Masazumi Takahashi, Yuichi Morohoshi, Naotaka Yamaguchi, Yuya Tsunoda, Hiroyuki Hayashi, Haruhiko Sugimura, Hirokazu KomatsuAbstract:A 41-year-old man with no familial history of gastric cancer was diagnosed as with intramucosal early gastric cancer. Two months after the first endoscopic submucosal dissection for signet-ring cell carcinoma (SRCC), the appearance of previously unrecognized multiple erosions of SRCC was noticed. Pathological examination after a total gastrectomy and Roux-en-Y reconstruction with D2 lymph node dissection were performed. Postoperative pathological examination revealed 90 and more lesions, which tempted the attending pathologist to refer to Genetic tests for the predisposition though the patient had no familial history of gastric cancer. There were no mutations in all the exons of CDH1 with conventional DNA sequencing, but multiplex ligation-dependent probe amplification, and reverse transcription-polymerase chain reaction analyses disclosed a large genomic deletion (c.1566-?_1711+?del), leading to the mRNA with loss of the exon 11. Among family members, his son was found to be a carrier of this change, while his parents were negative for the familial CDH1 mutation, implying that this change is a de novo event in the proband. The present report is the first description of a de novo large genomic deletion of CDH1 Gene associated with early-onset diffuse gastric cancer. When the clinician finds a relatively-young patient who has multiple SRCCs, CDH1 germline mutation should be considered, even for patients with no familial history.
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germline alterations in the CDH1 Gene in familial gastric cancer in the japanese population
Cancer Science, 2011Co-Authors: Hidetaka Yamada, Kazuya Shinmura, Hiroaki Ito, Masako Kasami, Naomi Sasaki, Hideyuki Shima, Masami Ikeda, Hong Tao, Masanori Goto, Takachika OzawaAbstract:Germline point or small frameshift mutations of the CDH1 (E-cadherin) Gene are known to cause familial gastric cancer (FGC), but the frequency of CDH1 mutations is low in Japanese patients with FGC. Because recent studies have reported germline large genomic deletions of CDH1 in European and Canadian patients with FGC, in the present study we examined DNA samples from 13 Japanese patients with FGC to determine whether similar germline changes were present in CDH1 in this population. Using a sequencing analysis, a 1-bp deletion (c.1212delC), leading to the production of a truncated protein (p.Asn405IlefsX12), was found in an FGC family; immunohistochemical analysis revealed the loss of CDH1 protein expression in the tumors in this family. Using a combination of multiplex ligation-dependent probe amplification (MLPA) and RT-PCR analyses, we also found a large genomic deletion (c.164-?_387+?del), leading to the loss of exon 3 and the production of a truncated protein (p.Val55GlyfsX38), in another FGC family. The functional effects of the detected mutations were examined using a slow aggregation assay. Significant impairment of cell–cell adhesion was detected in CHO-K1 cells expressing Ile405fsX12- and Gly55fsX38-type CDH1 compared with cells expressing wild-type CDH1. Our results suggest that the p.Asn405IlefsX12 and p.Val55GlyfsX38 mutations of the CDH1 Gene contribute to carcinoGenesis in patients with FGC. This is the first report of CDH1 germline truncating mutations in Japanese patients with FGC. Screening for large germline rearrangements should be included in CDH1 Genetic testing for FGC. (Cancer Sci 2011; 102: 1782–1788)
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absence of germline mono allelic promoter hypermethylation of the CDH1 Gene in gastric cancer patients
Molecular Cancer, 2009Co-Authors: Hidetaka Yamada, Kazuya Shinmura, Masanori Goto, Takachika Ozawa, Moriya Iwaizumi, Hiroyuki Konno, Hideki Kataoka, Masami Yamada, Toshihiro Tsuneyoshi, Fumihiko TaniokaAbstract:Background Germline mono-allelic promoter hypermethylation of the MLH1 or MSH2 Gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor Gene CDH1 (E-cadherin) might cause predisposition to gastric cancer.
Ken Tachibana - One of the best experts on this subject based on the ideXlab platform.
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5 aza 2 deoxycytidine reactivates the CDH1 Gene without influencing methylation of the entire cpg island or histone modification in a human cancer cell line
Proceedings of the Japan Academy. Series B Physical and Biological Sciences, 2004Co-Authors: Ken Tachibana, Ken Takeda, Masahiko ShiraishiAbstract:It is well-recognized that DNA methylation and histone modifications play critical roles in epiGenetic regulation of Gene activity through the alteration of chromatin structure. Recent studies have shown that in a subset of cancer cells, the silencing of the human E-cadherin (CDH1) Gene is associated with hypermethylation of the CpG island. However, the associated molecular mechanism remains unclear. To understand the mechanism, we have investigated the alteration of CpG island methylation and histone modifications during the reactivation of the CDH1 Gene by treatment with 5-aza-2'-deoxycytidine (5-aza-dC). Although the CDH1 Gene expression was recovered by treatment with 5-aza-dC in a liver cancer cell line Li21, the methylation status of the entire CpG island and acetylation and methylation status of associated histones were not significantly altered. These results demonstrate that the silenced CDH1 Gene can be reactivated without apparent alteration of histone modification or CpG island methylation. (Communicated by Takashi SUGIMURA, M.J.A.)
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heteroGeneity in the modification and involvement of chromatin components of the cpg island of the silenced human CDH1 Gene in cancer cells
Nucleic Acids Research, 2002Co-Authors: Shiro Koizume, Ken Tachibana, Takao Sekiya, Setsuo Hirohashi, Masahiko ShiraishiAbstract:The structural alteration of chromatin has a key role in regulating Gene expression. The alteration of chromatin is mediated by modification of its components. Detailed understanding of the relationship between these modifications, notably, methylation of the full-length CpG island, the association of methyl-CpG binding proteins (MBPs), and the acetylation and methylation of histones in Gene silencing is vitally important. Currently, however, the manner in which chromatin components, associated with a specific Gene, are modified is poorly understood. Here we provide in vivo evidence in cancer cells of the differential association between CpG methylation, MBPs, and histone modification in the entire CpG island of the human E-cadherin (CDH1) Gene. Of the cell lines with CDH1 transcriptional repression, the distribution of methyl-CpGs in the CpG island differed markedly. In a cell line with Gene silencing, the promoter region was almost methylation-free. Chromatin immunoprecipitation analysis revealed that the acetylation status of histone H4 differed between cell lines. However, deacetylated histone H3 was associated with the CpG island in all silenced cell lines. Binding of MeCP2 was also detected in all silenced cell lines. Additional binding of MBD1 protein was detected in a cell line in which the promoter region was poorly methylated and only histone H3 was deacetylated. Binding of MBD2 protein was detected in all other silenced cell lines. Histone H3 lysine 9 was methylated in all silenced cells, while histone H3 lysine 4 was methylated in some silenced cell lines. These results demonstrate that chromatin components associated with inactive CDH1 chromatin is heteroGeneously modified and suggests the presence of multiple pathways for the formation of inactive chromatin.
David G Huntsman - One of the best experts on this subject based on the ideXlab platform.
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hereditary diffuse gastric cancer diagnosis Genetic counseling and prophylactic total gastrectomy
Cancer, 2008Co-Authors: Henry T Lynch, Pardeep Kaurah, Debrah Wirtzfeld, Wendy S Rubinstein, Scott M Weissman, Jane F Lynch, William M Grady, Sara Wiyrick, Janine Senz, David G HuntsmanAbstract:Background A subset of patients with diffuse gastric cancer harbor deleterious cancer-causing germline mutations in the E-cadherin (CDH1) Gene, which predisposes to the autosomal dominantly inherited hereditary diffuse gastric cancer (HDGC) syndrome. These mutations are associated with a 70% life-time risk for diffuse gastric cancer (DGC) and, in addition, a 40% risk for lobular breast cancer in females. Management options for unaffected mutation carriers include prophylactic total gastrectomy.
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early gastric cancer in young asymptomatic carriers of germ line e cadherin mutations
The New England Journal of Medicine, 2001Co-Authors: David G Huntsman, Fatima Carneiro, Frank R Lewis, Patrick Macleod, Allen Hayashi, Kristin G Monaghan, Raymond Maung, Raquel Seruca, Charles E Jackson, Carlos CaldasAbstract:Background Germ-line truncating mutations in the E-cadherin (CDH1) Gene have been found in families with hereditary diffuse gastric cancer. These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance, predominantly in young persons. We describe Genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer. Methods Mutation-specific predictive Genetic testing was performed by polymerase-chain-reaction amplification, followed by restriction-enzyme digestion and DNA sequencing in Family 1 and by heteroduplex analysis in Family 2. A total gastrectomy was performed prophylactically in five carriers of mutations who were between 22 and 40 years old. In each case, the entire mucosa of the stomach was extensively sampled for microscopical analysis. Results Superficial infiltrates of malignant signet-ring cell...