Tumor Biology

, Volume 37, Issue 11, pp 14687–14699 | Cite as

Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease

  • Preeti Sharma
  • Shushruta Bhunia
  • Satish S. Poojary
  • Dinesh S. Tekcham
  • Mustafa Ahmed Barbhuiya
  • Sanjiv Gupta
  • Braj Raj Shrivastav
  • Pramod Kumar Tiwari
Original Article
First Online:
Received:
Accepted:

Abstract

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.

Keywords

DNA methylation Gallbladder cancer Gallstone disease Infinium 450K BeadChip Methylome profile 
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Notes

Acknowledgments

This study was supported by the Department of Science and Technology, Government of India, New Delhi, India (DST No. SR/SO/HS/0161/2010). We are thankful to laboratory members, Sonam Shrivastava and Anshu Agarwal for their assistance in mining the gene details. The authors are also thankful to the patients and their family members for their active cooperation in this study.

Compliance with ethical standards

Conflicts of interest

None.

Supplementary material

13277_2016_5355_MOESM1_ESM.xlsx (41 kb)
Supplementary file 1 List of common genes in all data sets (XLSX 41 kb)
13277_2016_5355_MOESM2_ESM.xlsx (10 kb)
Supplementary file 2 List of genes based on pathway Ontology (XLSX 10 kb)
13277_2016_5355_MOESM3_ESM.docx (11 kb)
Supplementary file 3 (DOCX 11 kb)
13277_2016_5355_MOESM4_ESM.docx (15 kb)
Supplementary file 4 (DOCX 14 kb)
13277_2016_5355_MOESM5_ESM.xlsx (79 kb)
Supplementary file 5 List of unique 903 genes found only in tumor-with-stone samples (XLSX 78 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Preeti Sharma
    • 1
  • Shushruta Bhunia
    • 1
  • Satish S. Poojary
    • 1
  • Dinesh S. Tekcham
    • 1
  • Mustafa Ahmed Barbhuiya
    • 1
    • 2
  • Sanjiv Gupta
    • 3
  • Braj Raj Shrivastav
    • 3
  • Pramod Kumar Tiwari
    • 1
  1. 1.Molecular and Human Genetics Division, Centre for GenomicsJiwaji UniversityGwaliorIndia
  2. 2.The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Cancer Hospital and Research InstituteGwaliorIndia

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