Quantitative analysis of CDKN2A methylation, mRNA, and p16(INK4a) protein expression in children and adolescents with Burkitt lymphoma: biological and clinical implications

Leuk Res. 2015 Feb;39(2):248-56. doi: 10.1016/j.leukres.2014.11.023. Epub 2014 Dec 9.

Abstract

CDKN2A is a tumor suppressor gene critical in the cell cycle regulation. Little is known regarding the role of CDKN2A methylation in the pathogenesis of Burkitt lymphoma (BL). CDKN2A methylation was investigated using pyrosequencing in 51 tumor samples. p16(INK4a) mRNA and protein levels were measured using real-time PCR and immunohistochemistry, respectively. CDKN2A methylation was detectable in 72% cases. Nuclear expression of p16(INK4a) was not detected in 41% cases. There was an association between methylation and absence of CDKN2A mRNA (P=0.003). In conclusion, CDKN2A methylation occurs at a high frequency suggesting a role in BL pathogenesis and potential therapeutic implications.

Keywords: Burkitt lymphoma; CDKN2A; Methylation; Pyrosequencing; Survival; p16(INK4a).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / metabolism*
  • Cell Line, Tumor
  • Child, Preschool
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • RNA, Messenger
  • RNA, Neoplasm