Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease.
Promoter methylation in various tumor suppressor genes is reported to influence gallbladder carcinogenesis. Here, we aimed to identify methylation status in gallbladder cancer (GBC) by performing a comprehensive genome-wide DNA methylation profiling. The methylation status of 485,577 CpG sites were investigated using Illumina's Infinium Human Methylation 450 BeadChip array in 24 tissues (eight each of tumor, adjacent non-tumor, and gallstone). About 33,443 differentially methylated sites (DMRs) were obtained in the whole human genome, of which 24,188 (72 %) were hypermethylated and 9255 (28 %) were hypomethylated. The data also revealed that majority of the DMRs are localized on the proximal promoter region [Transcription start sites (TSS200, TSS1500) and 5' untranslated region (5'UTR)] and first exon. Exclusion of first exon detected a total of 10,123 (79 %) hypermethylated and 2703 (21 %) hypomethylated sites. Comparative analysis of the later with our differential proteomics data resulted in identification of 7 hypermethylated or down-regulated (e.g., FBN1, LPP, and SOD3) and 61 hypomethylated or up-regulated markers (e.g., HBE1, SNRPF, TPD52) for GBC. These genes could be further validated on the basis of their methylation/expression status in order to identify their utility to be used as biomarker/s for early diagnosis and management of GBC.
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India.
Preeti
P
Sharma
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India.
Shushruta
S
Bhunia
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India.
Satish S
SS
Poojary
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India.
Dinesh S
DS
Tekcham
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India.|The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, MD, Baltimore, USA.
Mustafa Ahmed
MA
Barbhuiya
Cancer Hospital and Research Institute, Cancer Hills, Gwalior, Madhya Pradesh, 474009, India.
Sanjiv
S
Gupta
Cancer Hospital and Research Institute, Cancer Hills, Gwalior, Madhya Pradesh, 474009, India.
Braj Raj
BR
Shrivastav
Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India. pk_tiwari@hotmail.com.
Pramod Kumar
PK
Tiwari
D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D042882:Gallstones / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D024363:Transcription Initiation Site
D014408:Biomarkers, Tumor
DNA methylation; Gallbladder cancer; Gallstone disease; Infinium 450K BeadChip; Methylome profile