دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach.
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.
References: PLoS Genet. 2010 Jul 29;6(7):e1001043. (PMID: 20686660)
Nature. 2002 Jun 27;417(6892):949-54. (PMID: 12068308)
Transl Oncol. 2008 Mar;1(1):28-35. (PMID: 18607505)
Helicobacter. 2007 Apr;12(2):164-9. (PMID: 17309754)
Aliment Pharmacol Ther. 2004 Jul;20 Suppl 1:131-42. (PMID: 15298619)
Carcinogenesis. 2005 Oct;26(10):1698-705. (PMID: 15905200)
Cancer Sci. 2003 Oct;94(10):901-5. (PMID: 14556664)
Eur J Cancer. 2001 Oct;37 Suppl 8:S4-66. (PMID: 11602373)
Cancer Lett. 2013 Mar 1;330(1):33-40. (PMID: 23196062)
J Eval Clin Pract. 2007 Feb;13(1):79-85. (PMID: 17286727)
Clin Cancer Res. 2006 May 15;12(10):2995-3002. (PMID: 16707594)
Int J Oncol. 2012 Mar;40(3):739-46. (PMID: 22076605)
Nat Rev Cancer. 2004 Dec;4(12):988-93. (PMID: 15573120)
Science. 2004 Nov 26;306(5701):1568-71. (PMID: 15567866)
Diagn Mol Pathol. 2010 Dec;19(4):243-7. (PMID: 21051995)
Cancer Res. 1999 Nov 1;59(21):5438-42. (PMID: 10554013)
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):656-63. (PMID: 15701853)
Oncology (Williston Park). 2012 Feb;26(2):174, 213. (PMID: 22489352)
Cancer. 2006 Apr 1;106(7):1467-79. (PMID: 16518809)
J Gastroenterol Hepatol. 2007 Jul;22(7):970-2. (PMID: 17524038)
Sci Transl Med. 2012 Oct 17;4(156):156ra140. (PMID: 23076357)
J Pediatr Gastroenterol Nutr. 2007 Oct;45(4):428-32. (PMID: 18030208)
Lab Invest. 2008 Feb;88(2):161-70. (PMID: 18158559)
BMC Cancer. 2006 Dec 21;6:295. (PMID: 17184525)
Cancer Res. 2009 Aug 1;69(15):6315-21. (PMID: 19638575)
Nature. 2003 Oct 23;425(6960):846-51. (PMID: 14520411)
Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8681-6. (PMID: 10411935)
Cancer Sci. 2012 Jan;103(1):73-9. (PMID: 22017425)
Arq Gastroenterol. 2008 Apr-Jun;45(2):147-51. (PMID: 18622470)
Carcinogenesis. 2009 Mar;30(3):416-22. (PMID: 19126652)
Cell. 2006 Apr 21;125(2):301-13. (PMID: 16630818)
Oncogene. 2004 Aug 23;23(38):6329-40. (PMID: 15322508)
J Pathol. 2007 Oct;213(2):131-9. (PMID: 17724792)
Carcinogenesis. 2007 Feb;28(2):299-309. (PMID: 16861263)
Mol Cancer. 2009 Jun 03;8:31. (PMID: 19493342)
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. (PMID: 21296855)
Dig Dis Sci. 2010 Jun;55(6):1516-24. (PMID: 20437100)
Oncogene. 2000 Dec 14;19(54):6251-60. (PMID: 11175339)
Genome Biol. 2003;4(5):P3. (PMID: 12734009)
Helicobacter. 2011 Jun;16(3):179-88. (PMID: 21585603)
Am J Pathol. 2002 Mar;160(3):787-94. (PMID: 11891177)
J Clin Oncol. 2006 Jan 10;24(2):241-51. (PMID: 16330668)
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2317-21. (PMID: 17119066)
Genome Res. 2012 Feb;22(2):271-82. (PMID: 21659424)
J Pathol. 2003 May;200(1):23-31. (PMID: 12692837)
J Mol Diagn. 2008 Jan;10(1):13-27. (PMID: 18165277)
Hum Mol Genet. 2009 Dec 15;18(24):4808-17. (PMID: 19776032)
Genome Res. 2006 Mar;16(3):383-93. (PMID: 16449502)
BMC Cancer. 2010 May 21;10:227. (PMID: 20492682)
Nucleic Acids Res. 1999 Jan 1;27(1):29-34. (PMID: 9847135)
Genome Biol. 2003;4(10):R70. (PMID: 14519205)
Oncogene. 2007 Jul 12;26(32):4699-713. (PMID: 17297461)
Br J Cancer. 2005 Mar 28;92(6):1117-25. (PMID: 15770214)
Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):989-95. (PMID: 16467114)
PLoS One. 2012;7(4):e36275. (PMID: 22558417)
Int J Clin Oncol. 2008 Dec;13(6):498-503. (PMID: 19093176)
J Natl Cancer Inst. 2011 Jan 19;103(2):143-53. (PMID: 21163902)
Methods Mol Biol. 2009;507:149-63. (PMID: 18987813)
Cancer Sci. 2007 Dec;98(12):1853-61. (PMID: 17900260)
BMC Bioinformatics. 2008 Sep 09;9:365. (PMID: 18782434)
Nat Genet. 2006 Jul;38(7):787-93. (PMID: 16804544)
Cancer Prev Res (Phila). 2010 May;3(5):664-9. (PMID: 20424129)
Cancer. 2006 Mar 15;106(6):1250-9. (PMID: 16475210)
Mod Pathol. 1997 Mar;10(3):252-8. (PMID: 9071734)
Virchows Arch. 2010 Oct;457(4):415-22. (PMID: 20737169)
Gut. 2003 Apr;52(4):502-6. (PMID: 12631658)
Int J Cancer. 2009 Aug 1;125(3):666-73. (PMID: 19382179)
Int J Cancer. 2010 Dec 1;127(11):2588-97. (PMID: 20178103)
Nat Genet. 2002 Jun;31(2):141-9. (PMID: 11992124)
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
الوصف
تدمد:1471-230X
DOI:10.1186/1471-230X-14-55