دورية أكاديمية
DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach.
العنوان: | DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach. |
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المؤلفون: | Loh M, Liem N, Vaithilingam A, Lim PL, Sapari NS, Elahi E, Mok ZY, Cheng CL, Yan B, Pang B, Salto-Tellez M, Yong WP, Iacopetta B, Soong R; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. Richie_Soong@nus.edu.sg. |
المصدر: | BMC gastroenterology [BMC Gastroenterol] 2014 Mar 28; Vol. 14, pp. 55. Date of Electronic Publication: 2014 Mar 28. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100968547 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-230X (Electronic) Linking ISSN: 1471230X NLM ISO Abbreviation: BMC Gastroenterol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, [2001- |
مواضيع طبية MeSH: | CpG Islands* , DNA Methylation*, Adenocarcinoma/*genetics , Gene Expression Regulation, Neoplastic/*genetics , Stomach Neoplasms/*genetics, Adenocarcinoma/complications ; Adenocarcinoma/metabolism ; Age Factors ; Aged ; Case-Control Studies ; Cyclin A1/genetics ; Female ; Helicobacter Infections/complications ; Helicobacter pylori ; Homeodomain Proteins/genetics ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Male ; Membrane Proteins/genetics ; Microsatellite Instability ; Middle Aged ; Phenotype ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras) ; Sex Factors ; Signal Transduction ; Stomach Neoplasms/complications ; Stomach Neoplasms/metabolism ; ras Proteins/genetics |
مستخلص: | Background: Methylation-induced silencing of promoter CpG islands in tumor suppressor genes plays an important role in human carcinogenesis. In colorectal cancer, the CpG island methylator phenotype (CIMP) is defined as widespread and elevated levels of DNA methylation and CIMP+ tumors have distinctive clinicopathological and molecular features. In contrast, the existence of a comparable CIMP subtype in gastric cancer (GC) has not been clearly established. To further investigate this issue, in the present study we performed comprehensive DNA methylation profiling of a well-characterised series of primary GC. Methods: The methylation status of 1,421 autosomal CpG sites located within 768 cancer-related genes was investigated using the Illumina GoldenGate Methylation Panel I assay on DNA extracted from 60 gastric tumors and matched tumor-adjacent gastric tissue pairs. Methylation data was analysed using a recursively partitioned mixture model and investigated for associations with clinicopathological and molecular features including age, Helicobacter pylori status, tumor site, patient survival, microsatellite instability and BRAF and KRAS mutations. Results: A total of 147 genes were differentially methylated between tumor and matched tumor-adjacent gastric tissue, with HOXA5 and hedgehog signalling being the top-ranked gene and signalling pathway, respectively. Unsupervised clustering of methylation data revealed the existence of 6 subgroups under two main clusters, referred to as L (low methylation; 28% of cases) and H (high methylation; 72%). Female patients were over-represented in the H tumor group compared to L group (36% vs 6%; P = 0.024), however no other significant differences in clinicopathological or molecular features were apparent. CpG sites that were hypermethylated in group H were more frequently located in CpG islands and marked for polycomb occupancy. Conclusions: High-throughput methylation analysis implicates genes involved in embryonic development and hedgehog signaling in gastric tumorigenesis. GC is comprised of two major methylation subtypes, with the highly methylated group showing some features consistent with a CpG island methylator phenotype. |
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المشرفين على المادة: | 0 (CCNA1 protein, human) 0 (Cyclin A1) 0 (HOXA5 protein, human) 0 (Homeodomain Proteins) 0 (Intercellular Signaling Peptides and Proteins) 0 (KRAS protein, human) 0 (Membrane Proteins) 0 (Proto-Oncogene Proteins) 0 (SFRP1 protein, human) EC 2.7.11.1 (BRAF protein, human) EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) EC 3.6.5.2 (ras Proteins) |
تواريخ الأحداث: | Date Created: 20140329 Date Completed: 20141215 Latest Revision: 20211021 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC3986689 |
DOI: | 10.1186/1471-230X-14-55 |
PMID: | 24674026 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1471-230X |
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DOI: | 10.1186/1471-230X-14-55 |