CDKN2A promoter hypermethylation in astrocytomas is associated with age and sex

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Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)

Published on: September 26, 2015

Markênia Kélia Santos Alves1, Mário Henrique Girão Faria, Eduardo Henrique Cunha Neves Filho

  • 1Universidade Federal do Ceará, Department of Pathology and Forensic Medicine, Rua Alexandre Baraúna, 949, Porangabussu, CEP 60183-630 Fortaleza, Brazil. markenialves@yahoo.com.br

International Journal of Surgery (London, England)
|June 1, 2013
PubMed

Insights

CDKN2A promoter methylation frequently inactivates the CDKN2A gene in astrocytomas. This epigenetic alteration correlates with patient age and sex, impacting p16(INK4A) protein expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • CDKN2A (p16(INK4A)) inactivation is common in astrocytomas.
  • The precise mechanism of CDKN2A alteration in astrocytomas remains debated.
  • Promoter hypermethylation is a known cancer-related epigenetic modification.

Purpose of the Study:

  • To investigate the association between CDKN2A promoter methylation and p16(INK4A) expression in astrocytomas.
  • To correlate CDKN2A methylation status with tumor grade and clinicopathological parameters.
  • To elucidate the role of CDKN2A promoter methylation in astrocytoma pathogenesis.

Main Methods:

  • Analysis of 93 astrocytic tumors (WHO grades I-IV) using formalin-fixed paraffin-embedded tissue.
  • CDKN2A promoter methylation assessed via methylation-specific PCR.
  • p16(INK4A) protein expression evaluated by immunohistochemistry.

Main Results:

  • A strong negative correlation was observed between CDKN2A promoter methylation and p16(INK4A) expression (nuclear and cytoplasmic).
  • CDKN2A promoter methylation showed a significant negative correlation with patient age.
  • Female patients exhibited a higher frequency of CDKN2A methylated promoters compared to male patients (p=0.036).

Conclusions:

  • CDKN2A inactivation via promoter methylation is a frequent event in astrocytomas.
  • Patient age and sex are significant factors associated with CDKN2A promoter methylation in astrocytomas.
  • Epigenetic silencing of CDKN2A contributes to astrocytoma development and progression.
Keywords:
AgeAstrocytic tumorsCDKN2A MethylationExpressionp16

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