BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer

Rintaro Mikata1, Kenichi Fukai, Fumio Imazeki

  • 1Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

Oncology Reports
|April 30, 2010
PubMed

Insights

Aberrant methylation silences the BCL2L10 gene in gastric cancer, potentially contributing to tumor development. This gene silencing correlates with reduced BCL2L10 expression, suggesting its role in early gastric carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Aberrant methylation frequently silences tumor suppressor genes in gastric cancer.
  • BCL2L10, a pro-apoptotic gene, was previously shown to be repressed by promoter hypermethylation in gastric cancer cells.

Purpose of the Study:

  • To investigate the methylation status and expression of BCL2L10 in gastric cancer tissues.
  • To examine the methylation status of p16, RUNX3, and hMLH1 in gastric cancer.
  • To assess the association between gene methylation and EZH2 expression in gastric cancer.

Main Methods:

  • Methylation-specific PCR was used to analyze the methylation status of BCL2L10, p16, RUNX3, and hMLH1 in 21 gastric cancer tissues and corresponding non-neoplastic mucosae.
  • Gene expression levels were assessed.
  • The association between gene methylation and EZH2 expression was examined.

Main Results:

  • Aberrant BCL2L10 methylation was found in 38% of gastric cancers and 24% of non-neoplastic mucosae, correlating with low BCL2L10 expression.
  • Methylation frequencies for p16, RUNX3, and hMLH1 were consistent with previous reports.
  • EZH2 expression was significantly higher in tumors (48%) than in non-neoplastic mucosae (10%), but no significant correlation was found with the methylation of the studied genes.

Conclusions:

  • Silencing of BCL2L10 by aberrant methylation is a common event in gastric cancer.
  • BCL2L10 inactivation may play a role in the early stages of gastric carcinogenesis.

Related Concept Videos

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...
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.
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...
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Gastritis II: Pathophysiology01:26

Gastritis II: Pathophysiology

The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly via the oral-oral route through saliva or shared utensils, and can also be transmitted in overcrowded or unhygienic environments through contaminated water, despite its brief survival outside the body.ColonizationOnce ingested, H. pylori enters the stomach and begins colonization by navigating through the mucus layer lining the stomach wall. It...