Frequent epigenetic inactivation of RASSF10 in thyroid cancer

Undraga Schagdarsurengin1, Antje M Richter, Christina Wöhler

  • 1Institute for Genetics, Justus-Liebig-University, Giessen, Germany.

Epigenetics
|November 26, 2009
PubMed

Insights

Ras association domain family 10 (RASSF10) acts as a tumor suppressor. Frequent epigenetic silencing of RASSF10 was observed in thyroid cancer, suggesting its role in thyroid carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The Ras association domain family (RASSF) comprises tumor suppressor genes, with several members frequently silenced in human cancers.
  • Epigenetic alterations, particularly DNA methylation, play a crucial role in cancer development.

Purpose of the Study:

  • To investigate the role of a novel RASSF member, RASSF10, in thyroid carcinogenesis.
  • To determine the frequency and significance of RASSF10 epigenetic inactivation in thyroid tumors.

Main Methods:

  • Analysis of RASSF10 CpG island promoter methylation in thyroid cancer cell lines and primary tumors.
  • Comparison of RASSF10 methylation levels between cancerous and non-cancerous thyroid tissues.
  • Correlation of RASSF10 methylation with gene expression and lymph node status.
  • Assessment of RASSF10 transcriptional reactivation upon DNA methylation inhibitor treatment.

Main Results:

  • Intensive methylation of the RASSF10 promoter was found in nine thyroid cancer cell lines and 66% of primary thyroid carcinomas.
  • RASSF10 methylation was significantly increased in primary thyroid carcinomas compared to normal thyroid and follicular adenoma (p < 0.004).
  • Hypermethylation of RASSF10 was significantly associated with cancerous lymph nodes (79% vs. 36%, p = 0.047).
  • RASSF10 promoter hypermethylation correlated with reduced gene expression, and DNA methylation inhibitor treatment reactivated RASSF10 transcription.

Conclusions:

  • Frequent epigenetic inactivation of RASSF10 occurs in thyroid cancer.
  • RASSF10 functions as a potential tumor suppressor gene epigenetically silenced during thyroid carcinogenesis.
  • RASSF10 represents a novel candidate tumor suppressor gene in thyroid cancer development.

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.
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...
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...