Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Gastroenterology
Published in: BMC Gastroenterology 1/2014

Open Access 01-12-2014 | Research article

DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach

Authors: Marie Loh, Natalia Liem, Aparna Vaithilingam, Pei Li Lim, Nur Sabrina Sapari, Eiram Elahi, Zuan Yu Mok, Chee Leong Cheng, Benedict Yan, Brendan Pang, Manuel Salto-Tellez, Wei Peng Yong, Barry Iacopetta, Richie Soong

Published in: BMC Gastroenterology | Issue 1/2014

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
Yeoh KG: How do we improve outcomes for gastric cancer?. J Gastroenterol Hepatol. 2007, 22 (7): 970-972. 10.1111/j.1440-1746.2007.04956.x.CrossRefPubMed
2.
Chie WC, Chang YH, Chen HH: A novel method for evaluation of improved survival trend for common cancer: early detection or improvement of medical care. J Eval Clin Pract. 2007, 13 (1): 79-85. 10.1111/j.1365-2753.2006.00656.x.CrossRefPubMed
3.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed
4.
Chen J, Bu XL, Wang QY, Hu PJ, Chen MH: Decreasing seroprevalence of Helicobacter pylori infection during 1993–2003 in Guangzhou, southern China. Helicobacter. 2007, 12 (2): 164-169. 10.1111/j.1523-5378.2007.00487.x.CrossRefPubMed
5.
Kawakami E, Machado RS, Ogata SK, Langner M: Decrease in prevalence of Helicobacter pylori infection during a 10-year period in Brazilian children. Arq Gastroenterol. 2008, 45 (2): 147-151.CrossRefPubMed
6.
Tkachenko MA, Zhannat NZ, Erman LV, Blashenkova EL, Isachenko SV, Isachenko OB, Graham DY, Malaty HM: Dramatic changes in the prevalence of Helicobacter pylori infection during childhood: a 10-year follow-up study in Russia. J Pediatr Gastroenterol Nutr. 2007, 45 (4): 428-432. 10.1097/MPG.0b013e318064589f.CrossRefPubMed
7.
Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, Malvezzi M, La Vecchia C: Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009, 125 (3): 666-673. 10.1002/ijc.24290.CrossRefPubMed
8.
9.
Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001, 37 (Suppl 8): S4-S66.CrossRefPubMed
10.
Christensen BC, Kelsey KT, Zheng S, Houseman EA, Marsit CJ, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Kushi LH, Kwan ML, Wiencke JK: Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake. PLoS Genet. 2010, 6 (7): e1001043-10.1371/journal.pgen.1001043.CrossRefPubMedPubMedCentral
11.
Christensen BC, Marsit CJ, Houseman EA, Godleski JJ, Longacker JL, Zheng S, Yeh RF, Wrensch MR, Wiemels JL, Karagas MR, Bueno R, Sugarbaker DJ, Nelson HH, Wiencke JK, Kelsey KT: Differentiation of lung adenocarcinoma, pleural mesothelioma, and nonmalignant pulmonary tissues using DNA methylation profiles. Cancer Res. 2009, 69 (15): 6315-6321. 10.1158/0008-5472.CAN-09-1073.CrossRefPubMedPubMedCentral
12.
Christensen BC, Smith AA, Zheng S, Koestler DC, Houseman EA, Marsit CJ, Wiemels JL, Nelson HH, Karagas MR, Wrensch MR, Kelsey KT, Wiencke JK: DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma. J Natl Cancer Inst. 2010, 103 (2): 143-153.CrossRefPubMed
13.
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP: CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999, 96 (15): 8681-8686. 10.1073/pnas.96.15.8681.CrossRefPubMedPubMedCentral
14.
Issa JP: CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004, 4 (12): 988-993. 10.1038/nrc1507.CrossRefPubMed
15.
16.
Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, Kang GH, Widschwendter M, Weener D, Buchanan D, Koh H, Simms L, Barker M, Leggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006, 38 (7): 787-793. 10.1038/ng1834.CrossRefPubMed
17.
Enomoto S, Maekita T, Tsukamoto T, Nakajima T, Nakazawa K, Tatematsu M, Ichinose M, Ushijima T: Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non-cancerous gastric mucosae. Cancer Sci. 2007, 98 (12): 1853-1861. 10.1111/j.1349-7006.2007.00625.x.CrossRefPubMed
18.
Kusano M, Toyota M, Suzuki H, Akino K, Aoki F, Fujita M, Hosokawa M, Shinomura Y, Imai K, Tokino T: Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus. Cancer. 2006, 106 (7): 1467-1479. 10.1002/cncr.21789.CrossRefPubMed
19.
Park SY, Kook MC, Kim YW, Cho NY, Jung N, Kwon HJ, Kim TY, Kang GH: CpG island hypermethylator phenotype in gastric carcinoma and its clinicopathological features. Virchows Arch. 2010, 457 (4): 415-422. 10.1007/s00428-010-0962-0.CrossRefPubMed
20.
An C, Choi IS, Yao JC, Worah S, Xie K, Mansfield PF, Ajani JA, Rashid A, Hamilton SR, Wu TT: Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clin Cancer Res. 2005, 11 (2 Pt 1): 656-663.PubMed
21.
Oue N, Mitani Y, Motoshita J, Matsumura S, Yoshida K, Kuniyasu H, Nakayama H, Yasui W: Accumulation of DNA methylation is associated with tumor stage in gastric cancer. Cancer. 2006, 106 (6): 1250-1259. 10.1002/cncr.21754.CrossRefPubMed
22.
Oue N, Oshimo Y, Nakayama H, Ito R, Yoshida K, Matsusaki K, Yasui W: DNA methylation of multiple genes in gastric carcinoma: association with histological type and CpG island methylator phenotype. Cancer Sci. 2003, 94 (10): 901-905. 10.1111/j.1349-7006.2003.tb01373.x.CrossRefPubMed
23.
Kang GH, Lee S, Cho NY, Gandamihardja T, Long TI, Weisenberger DJ, Campan M, Laird PW: DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest. 2008, 88 (2): 161-170. 10.1038/labinvest.3700707.CrossRefPubMed
24.
Kang GH, Lee S, Kim WH, Lee HW, Kim JC, Rhyu MG, Ro JY: Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma. Am J Pathol. 2002, 160 (3): 787-794. 10.1016/S0002-9440(10)64901-2.CrossRefPubMedPubMedCentral
25.
Chen HY, Zhu BH, Zhang CH, Yang DJ, Peng JJ, Chen JH, Liu FK, He YL: High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer. Cancer Sci. 2011, 103 (1): 73-79.CrossRefPubMed
26.
Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, Baylin SB, Issa JP: Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999, 59 (21): 5438-5442.PubMed
27.
Sapari NS, Loh M, Vaithilingam A, Soong R: Clinical potential of DNA methylation in gastric cancer: a meta-analysis. PLoS One. 2012, 7 (4): e36275-10.1371/journal.pone.0036275.CrossRefPubMedPubMedCentral
28.
Loh M, Liem N, Lim PL, Vaithilingam A, Cheng CL, Salto-Tellez M, Yong WP, Soong R: Impact of sample heterogeneity on methylation analysis. Diagn Mol Pathol. 2010, 19 (4): 243-247. 10.1097/PDM.0b013e3181de4396.CrossRefPubMed
29.
Soong R, Iacopetta BJ: A rapid and nonisotopic method for the screening and sequencing of p53 gene mutations in formalin-fixed, paraffin-embedded tumors. Mod Pathol. 1997, 10 (3): 252-258.PubMed
30.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, et al: Mutations of the BRAF gene in human cancer. Nature. 2002, 417 (6892): 949-954. 10.1038/nature00766.CrossRefPubMed
31.
Krypuy M, Newnham GM, Thomas DM, Conron M, Dobrovic A: High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer. BMC Cancer. 2006, 6: 295-10.1186/1471-2407-6-295.CrossRefPubMedPubMedCentral
32.
Buhard O, Cattaneo F, Wong YF, Yim SF, Friedman E, Flejou JF, Duval A, Hamelin R: Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol. 2006, 24 (2): 241-251.CrossRefPubMed
33.
Bibikova M, Fan JB: GoldenGate assay for DNA methylation profiling. Methods Mol Biol. 2009, 507: 149-163. 10.1007/978-1-59745-522-0_12.CrossRefPubMed
34.
Houseman EA, Christensen BC, Yeh RF, Marsit CJ, Karagas MR, Wrensch M, Nelson HH, Wiemels J, Zheng S, Wiencke JK, Kelsey KT: Model-based clustering of DNA methylation array data: a recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions. BMC Bioinformatics. 2008, 9: 365-10.1186/1471-2105-9-365.CrossRefPubMedPubMedCentral
35.
Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RA, Laird PW: Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2011, 22 (2): 271-282.CrossRefPubMed
36.
Calinski RB, Harabasz J: A dendrite method for cluster analysis. Comm Stat. 1974, 3: 1-27.CrossRef
37.
Bibikova M, Lin Z, Zhou L, Chudin E, Garcia EW, Wu B, Doucet D, Thomas NJ, Wang Y, Vollmer E, Goldmann T, Seifart C, Jiang W, Barker DL, Chee MS, Floros J, Fan JB: High-throughput DNA methylation profiling using universal bead arrays. Genome Res. 2006, 16 (3): 383-393. 10.1101/gr.4410706.CrossRefPubMedPubMedCentral
38.
Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995, 57: 289-300.
39.
Ang PW, Loh M, Liem N, Lim PL, Grieu F, Vaithilingam A, Platell C, Yong WP, Iacopetta B, Soong R: Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer. 2010, 10: 227-10.1186/1471-2407-10-227.CrossRefPubMedPubMedCentral
40.
Hosack DA, Dennis G, Sherman BT, Lane HC, Lempicki RA: Identifying biological themes within lists of genes with EASE. Genome Biol. 2003, 4 (10): R70-10.1186/gb-2003-4-10-r70.CrossRefPubMedPubMedCentral
41.
Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003, 4 (5): 3-10.1186/gb-2003-4-5-p3.CrossRef
42.
Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M: KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 1999, 27 (1): 29-34. 10.1093/nar/27.1.29.CrossRefPubMedPubMedCentral
43.
Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, Koseki H, Fuchikami T, Abe K, Murray HL, Zucker JP, Yuan B, Bell GW, Herbolsheimer E, Hannett NM, Sun K, Odom DT, Otte AP, Volkert TL, Bartel DP, Melton DA, Gifford DK, Jaenisch R, Young RA: Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 2006, 125 (2): 301-313. 10.1016/j.cell.2006.02.043.CrossRefPubMedPubMedCentral
44.
Kim TY, Jong HS, Jung Y, Kim TY, Kang GH, Bang YJ: DNA hypermethylation in gastric cancer. Aliment Pharmacol Ther. 2004, 20 (Suppl 1): 131-142.CrossRefPubMed
45.
Marsit CJ, Christensen BC, Houseman EA, Karagas MR, Wrensch MR, Yeh RF, Nelson HH, Wiemels JL, Zheng S, Posner MR, McClean MD, Wiencke JK, Kelsey KT: Epigenetic profiling reveals etiologically distinct patterns of DNA methylation in head and neck squamous cell carcinoma. Carcinogenesis. 2009, 30 (3): 416-422. 10.1093/carcin/bgp006.CrossRefPubMedPubMedCentral
46.
McRonald FE, Morris MR, Gentle D, Winchester L, Baban D, Ragoussis J, Clarke NW, Brown MD, Kishida T, Yao M, Latif F, Maher ER: CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma. Mol Cancer. 2009, 8: 31-10.1186/1476-4598-8-31.CrossRefPubMedPubMedCentral
47.
Moran A, Fernandez-Marcelo T, Carro J, De Juan C, Pascua I, Head J, Gomez A, Hernando F, Torres AJ, Benito M, Iniesta P: Methylation profiling in non-small cell lung cancer: clinical implications. Int J Oncol. 2011, 40 (3): 739-746.PubMed
48.
Shin CM, Kim N, Jung Y, Park JH, Kang GH, Park WY, Kim JS, Jung HC, Song IS: Genome-wide DNA methylation profiles in noncancerous gastric mucosae with regard to Helicobacter pylori infection and the presence of gastric cancer. Helicobacter. 2011, 16 (3): 179-188. 10.1111/j.1523-5378.2011.00838.x.CrossRefPubMed
49.
Iacopetta B, Kawakami K, Watanabe T: Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive subgroup?. Int J Clin Oncol. 2008, 13 (6): 498-503. 10.1007/s10147-008-0854-3.CrossRefPubMed
50.
Chang MS, Uozaki H, Chong JM, Ushiku T, Sakuma K, Ishikawa S, Hino R, Barua RR, Iwasaki Y, Arai K, Fujii H, Nagai H, Fukayama M: CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Cancer Res. 2006, 12 (10): 2995-3002. 10.1158/1078-0432.CCR-05-1601.CrossRefPubMed
51.
Zhang KL, Sun Y, Li Y, Liu M, Qu B, Cui SH, Kong QY, Chen XY, Li H, Liu J: Increased frequency of CpG island methylator phenotype and CDH1 methylation in a gastric cancer high-risk region of china. Transl Oncol. 2008, 1 (1): 28-35. 10.1593/tlo.07103.CrossRefPubMedPubMedCentral
52.
Kim H, Kim YH, Kim SE, Kim NG, Noh SH: Concerted promoter hypermethylation of hMLH1, p16INK4A, and E-cadherin in gastric carcinomas with microsatellite instability. J Pathol. 2003, 200 (1): 23-31. 10.1002/path.1325.CrossRefPubMed
53.
Kim JG, Takeshima H, Niwa T, Rehnberg E, Shigematsu Y, Yoda Y, Yamashita S, Kushima R, Maekita T, Ichinose M, Katai H, Park WS, Hong YS, Park CH, Ushijima T: Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers. Cancer Lett. 2013, 330 (1): 33-40. 10.1016/j.canlet.2012.11.022.CrossRefPubMed
54.
Zouridis H, Deng N, Ivanova T, Zhu Y, Wong B, Huang D, Wu YH, Wu Y, Tan IB, Liem N, Gopalakrishnan V, Luo Q, Wu J, Lee M, Yong WP, Goh LK, Teh BT, Rozen S, Tan P: Methylation subtypes and large-scale epigenetic alterations in gastric cancer. Sci Transl Med. 2012, 4 (156)): 156ra140-PubMed
55.
Byun HM, Siegmund KD, Pan F, Weisenberger DJ, Kanel G, Laird PW, Yang AS: Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Hum Mol Genet. 2009, 18 (24): 4808-4817. 10.1093/hmg/ddp445.CrossRefPubMedPubMedCentral
56.
Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN, Beachy PA: Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003, 425 (6960): 846-851. 10.1038/nature01972.CrossRefPubMed
57.
Taniguchi H, Yamamoto H, Akutsu N, Nosho K, Adachi Y, Imai K, Shinomura Y: Transcriptional silencing of hedgehog-interacting protein by CpG hypermethylation and chromatic structure in human gastrointestinal cancer. J Pathol. 2007, 213 (2): 131-139. 10.1002/path.2216.CrossRefPubMed
58.
Vismodegib granted FDA approval for treatment of basal cell carcinoma. Oncology. 2012, 26 (2): 174-213.
59.
Strathdee G, Sim A, Soutar R, Holyoake TL, Brown R: HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia. Carcinogenesis. 2007, 28 (2): 299-309.CrossRefPubMed
60.
Ma X, Chen K, Huang S, Zhang X, Adegboyega PA, Evers BM, Zhang H, Xie J: Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis. 2005, 26 (10): 1698-1705. 10.1093/carcin/bgi130.CrossRefPubMed
61.
Martin J, Donnelly JM, Houghton J, Zavros Y: The role of sonic hedgehog reemergence during gastric cancer. Dig Dis Sci. 2010, 55 (6): 1516-1524. 10.1007/s10620-010-1252-z.CrossRefPubMed
62.
Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC: Gastric cancer originating from bone marrow-derived cells. Science. 2004, 306 (5701): 1568-1571. 10.1126/science.1099513.CrossRefPubMed
63.
Nojima M, Suzuki H, Toyota M, Watanabe Y, Maruyama R, Sasaki S, Sasaki Y, Mita H, Nishikawa N, Yamaguchi K, Hirata K, Itoh F, Tokino T, Mori M, Imai K, Shinomura Y: Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer. Oncogene. 2007, 26 (32): 4699-4713. 10.1038/sj.onc.1210259.CrossRefPubMed
64.
Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB: A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet. 2002, 31 (2): 141-149. 10.1038/ng892.CrossRefPubMed
65.
Nishioka M, Kohno T, Takahashi M, Niki T, Yamada T, Sone S, Yokota J: Identification of a 428-kb homozygously deleted region disrupting the SEZ6L gene at 22q12.1 in a lung cancer cell line. Oncogene. 2000, 19 (54): 6251-6260. 10.1038/sj.onc.1204031.CrossRefPubMed
66.
Raji OY, Agbaje OF, Duffy SW, Cassidy A, Field JK: Incorporation of a genetic factor into an epidemiologic model for prediction of individual risk of lung cancer: the Liverpool Lung Project. Cancer Prev Res (Phila). 2010, 3 (5): 664-669. 10.1158/1940-6207.CAPR-09-0141.CrossRef
67.
Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M, Tamura G, Saito D, Sugimura T, Ichinose M, Ushijima T: High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006, 12 (3 Pt 1): 989-995.CrossRefPubMed
68.
Nakajima T, Maekita T, Oda I, Gotoda T, Yamamoto S, Umemura S, Ichinose M, Sugimura T, Ushijima T, Saito D: Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Canc Epidemiol Biomarkers Prev: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2006, 15 (11): 2317-2321. 10.1158/1055-9965.EPI-06-0436.CrossRef
69.
Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, Hui WM, Rashid A, Kwong YL: Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut. 2003, 52 (4): 502-506. 10.1136/gut.52.4.502.CrossRefPubMedPubMedCentral
70.
Dote H, Toyooka S, Tsukuda K, Yano M, Ota T, Murakami M, Naito M, Toyota M, Gazdar AF, Shimizu N: Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in gastrointestinal tumour. Br J Cancer. 2005, 92 (6): 1117-1125. 10.1038/sj.bjc.6602458.CrossRefPubMedPubMedCentral
71.
Schneider BG, Peng DF, Camargo MC, Piazuelo MB, Sicinschi LA, Mera R, Romero-Gallo J, Delgado AG, Bravo LE, Wilson KT, Peek RM, Correa P, El-Rifai W: Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. Int J Cancer. 2010, 127 (11): 2588-2597. 10.1002/ijc.25274.CrossRefPubMedPubMedCentral
Metadata
Title
DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach
Authors
Marie Loh
Natalia Liem
Aparna Vaithilingam
Pei Li Lim
Nur Sabrina Sapari
Eiram Elahi
Zuan Yu Mok
Chee Leong Cheng
Benedict Yan
Brendan Pang
Manuel Salto-Tellez
Wei Peng Yong
Barry Iacopetta
Richie Soong
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2014
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-14-55

Other articles of this Issue 1/2014

BMC Gastroenterology 1/2014 Go to the issue

Case report

Orthotopic liver transplantation in situs inversus adult from an ABO-incompatible donor with situs inversus

Research article

Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children

Research article

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses

Research article

Overexpression of SLC38A1 is associated with poorer prognosis in Chinese patients with gastric cancer

Research article

Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release

Research article

Long intestinal tube splinting prevents postoperative adhesive small-bowel obstruction in sclerosing encapsulating peritonitis
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits