Related Experiment Video

Updated: May 30, 2026

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation

Jean Charles Nault1, Monique Fabre, Gabrielle Couchy

  • 1Inserm, U674, Génomique fonctionnelle des tumeurs solides, Paris, France.

Journal of Hepatology
|August 13, 2011
PubMed
Abstract

Insights

Somatic G-protein alpha-subunit (GNAS)-activating mutations are linked to McCune-Albright syndrome and found in liver tumors. These mutations activate inflammatory pathways and STAT3, contributing to liver tumorigenesis.

Area of Science:

  • Hepatology
  • Oncology
  • Molecular Biology

Background:

  • Mosaic G-protein alpha-subunit (GNAS)-activating mutations cause McCune-Albright (MCA) syndrome.
  • GNAS mutations are implicated in various tumor types, leading to cyclic-AMP accumulation.
  • Hepatocellular adenoma (HCA) in MCA patients prompted investigation of GNAS in liver carcinogenesis.

Purpose of the Study:

  • To investigate GNAS mutations in benign and malignant liver tumors.
  • To explore the association between GNAS mutations and liver carcinogenesis.
  • To understand the role of GNAS in hepatocellular adenoma and carcinoma.

Main Methods:

  • Screening for GNAS mutations in 164 HCA, 245 hepatocellular carcinoma (HCC), and 17 fibrolamellar carcinomas via sequencing.
  • Characterization of tumors using quantitative RT-PCR, gene mutation screening, and pathological review.
  • Analysis of wild-type and mutant GNAS expression consequences in hepatocellular cell lines.

Main Results:

  • Somatic GNAS-activating mutations were found in 5 benign tumors and 2 HCC.
  • GNAS mutations were exclusive of HNF1A, CTNNB1, and IL6ST in benign tumors, but co-occurred with CTNNB1 in one HCC.
  • GNAS-mutated tumors exhibited an inflammatory phenotype with fibrosis and STAT3 activation, linked to IL-6 and interferon pathway activation.

Conclusions:

  • First identification of an association between MCA syndrome and HCA occurrence.
  • Somatic GNAS-activating mutations in sporadic liver tumors are characterized by an inflammatory phenotype.
  • Demonstrated cross-talk between cyclic-AMP and JAK/STAT pathways, reinforcing STAT3's role in liver tumorigenesis.

Related Concept Videos

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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...