Related Experiment Video

Updated: Jul 5, 2026

Methyl-binding DNA capture Sequencing for Patient Tissues
08:40

Methyl-binding DNA capture Sequencing for Patient Tissues

Published on: October 31, 2016

Promoter hypermethylation and reduced expression of RASSF1A are frequent molecular alterations of endometrial

Judit Pallarés1, Ana Velasco, Nuria Eritja

  • 1Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain. jpallares@arnau.scs.es

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|May 13, 2008
PubMed

Insights

Reduced expression of the RASSF1A tumor suppressor gene is common in endometrial cancer, often due to promoter methylation. This downregulation correlates with microsatellite instability and advanced stages, suggesting a role in cancer development via the RAS-MAPK pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alterations in the RAS-MAPK pathway are frequent in endometrial carcinoma.
  • RASSF1A, a tumor suppressor gene, negatively regulates this pathway and can be inactivated by promoter methylation.
  • Reduced RASSF1A expression is observed in various human tumors.

Purpose of the Study:

  • To assess immunohistochemical expression of RASSF1A in normal endometrium and endometrial carcinoma.
  • To correlate RASSF1A expression with K-RAS mutations, microsatellite instability, RASSF1A promoter methylation, and clinicopathological data.

Main Methods:

  • Immunohistochemical evaluation of RASSF1A expression on tissue microarrays from 80 normal endometrium and 157 endometrial carcinoma samples.
  • Assessment of RASSF1A promoter methylation using methylation-specific PCR.
  • Correlation analysis with K-RAS mutations, microsatellite instability, cell proliferation markers (Ki67, Cyclin D1), and clinicopathological data.

Main Results:

  • RASSF1A expression was significantly reduced in 48% of endometrial carcinomas, particularly those with microsatellite instability.
  • RASSF1A promoter methylation was found in 74% of endometrial carcinomas and frequently associated with reduced RASSF1A expression.
  • RASSF1A promoter hypermethylation was more common in advanced-stage endometrial carcinoma.

Conclusions:

  • Reduced RASSF1A expression, often driven by promoter methylation, is a significant event in endometrial carcinogenesis.
  • Downregulation of RASSF1A may contribute to endometrial cancer development by affecting cell proliferation and apoptosis through the MAPK pathway.

Related Concept Videos

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...
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...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...