High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors

Arch Oral Biol. 2015 Nov;60(11):1662-6. doi: 10.1016/j.archoralbio.2015.08.011. Epub 2015 Aug 22.


Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands.

Materials and methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations.

Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms - between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P=0.00), and significantly decreased in comparison to the carcinoma group (P=0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P=0.044 and P=0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P=0.013).

Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and p14(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands.

Keywords: Parotid gland tumors; Promoter hypermethylation; Telomere length; p14; p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Pleomorphic / genetics*
  • Adenoma, Pleomorphic / metabolism
  • Adenoma, Pleomorphic / pathology
  • Adult
  • Aged
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Methylation*
  • Female
  • Genes, Tumor Suppressor
  • Genes, p16*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Parotid Neoplasms / genetics*
  • Parotid Neoplasms / metabolism
  • Parotid Neoplasms / pathology
  • Promoter Regions, Genetic
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Homeostasis
  • Young Adult


  • CDK2AP2 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Oncogene Proteins