title: Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG methylation in gastric cancer.
abstract: BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a prominent role in B-cell development. Genetic polymorphisms within a single locus encoding BACH2 are associated with various autoimmune diseases and allergies. In this study, restriction landmark genomic scanning revealed methylation at a NotI site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and primary gastric tumors. Increased methylation of the BACH2 promoter was observed in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was significantly associated with decreased gene expression. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin. A restored BACH2 expression in BACH2-silenced gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e. RNA interference) increased cell proliferation in gastric cancer cells. Clinicopathologic data showed that decreased BACH2 expression occurred significantly more frequently in intestinal-type (27/44, 61%) compared with diffuse-type (13/50, 26%) gastric cancers (P<0.001). Furthermore, BACH2 promoter methylation paralleled that of previously identified targets, such as LRRC3B, LIMS2, PRKD1 and POPDC3, in a given set of gastric tumors. We propose that concerted methylation in many promoters plays a role in accelerating gastric tumor formation and that methylated promoter loci may be targets for therapeutic treatment, such as the recently introduced technique of epigenetic editing.
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Keeok
authors.initials: K
authors.lastname: Haam
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Mirang
authors.initials: M
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Seung-Moo
authors.initials: SM
authors.lastname: Noh
authors.affiliation: College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Song
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea. Electronic address: yongsung@kribb.re.kr.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors
keywords: BACH2; Concerted methylation; Gastric cancer; RLGS