title: Dysfunction of subtelomeric methylation and telomere length in gallstone disease and gallbladder cancer patients of North Central India.
abstract: BACKGROUND
  Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones.
  
  
  METHODS
  Relative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non-tumor.
  
  
  RESULTS
  We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones.
  
  
  CONCLUSIONS
  This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels.
authors: Department of Molecular and Human Genetics, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors: Satish S
authors: SS
authors: Poojary
authors: Department of Molecular and Human Genetics, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors: Gunja
authors: G
authors: Mishra
authors: Department of Pathology, Cancer Hospital and Research Institute, Gwalior, Madhya Pradesh, India.
authors: Sanjiv
authors: S
authors: Gupta
authors: Department of Oncology, Cancer Hospital and Research Institute, Gwalior, Madhya Pradesh, India.
authors: Braj Raj
authors: BR
authors: Shrivastav
authors: Department of Molecular and Human Genetics, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors: Pramod Kumar
authors: PK
authors: Tiwari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005706:Gallbladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D042882:Gallstones / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D016615:Telomere; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm
keywords: Gallbladder cancer; Gallstones; Methylation; Subtelomere; Telomere