Related Experiment Video

Updated: Jul 17, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas

Atsuo Yoshino1, Yoichi Katayama, Akiyoshi Ogino

  • 1Department of Neurological Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan. ayoshino@med.nihon-u.ac.jp

Journal of Neuro-Oncology
|January 12, 2007
PubMed

Insights

Aberrant promoter hypermethylation of cell cycle genes, particularly RB1 pathway genes, is frequent in pituitary adenomas. The p16(INK4a) gene showed the most common deregulation, impacting tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant DNA methylation, specifically CpG island hypermethylation in promoter regions, is a known mechanism for gene silencing.
  • This epigenetic alteration plays a critical role in the dysregulation of cell cycle control, contributing to tumorigenesis.
  • The specific contribution of cell cycle gene promoter methylation to pituitary adenoma development remains incompletely understood.

Purpose of the Study:

  • To investigate the prevalence and significance of promoter methylation in key cell cycle regulatory genes within pituitary adenomas.
  • To identify specific genes and pathways frequently affected by hypermethylation in these tumors.
  • To explore potential correlations between methylation status and clinicopathological features.

Main Methods:

  • Profiling of CpG island methylation status for RB1, p14(ARF), p15(INK4b), p16(INK4a), p21(Waf1/Cip1), p27(Kip1), and p73 genes.
  • Analysis conducted on 34 pituitary adenoma samples using methylation-specific polymerase chain reaction (PCR) assays.
  • Statistical analysis to assess correlations between methylation patterns and clinicopathological data.

Main Results:

  • Promoter hypermethylation was detected in RB1 (35%), p14(ARF) (6%), p15(INK4b) (32%), p16(INK4a) (59%), p21(Waf1/Cip1) (3%), p27(Kip1) (0%), and p73 (12%) genes.
  • A high overall frequency of methylation (88%) was observed, with at least one cell cycle gene methylated in most adenomas, particularly RB1 pathway genes (85%).
  • RB1 and p16(INK4a) methylation were often mutually exclusive, while p15(INK4b) methylation coincided with RB1 and/or p16(INK4a).

Conclusions:

  • Aberrant hypermethylation of critical cell cycle regulatory genes is a common event in pituitary adenomas.
  • The RB1 pathway genes are frequently targeted, with p16(INK4a) promoter hypermethylation being the most prevalent alteration.
  • While specific methylation patterns exist, no significant correlation was found between methylation status and clinicopathological features, suggesting a primary role in initial tumorigenesis.

More Related Videos

Methyl-binding DNA capture Sequencing for Patient Tissues08:40

Methyl-binding DNA capture Sequencing for Patient Tissues

Published on: October 31, 2016

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images09:42

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...