Gastrointestinal Stromal Tumor Pathogenesis

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal (GI) tract. It’s a type of cancer that starts in special cells in the wall of the GI tract, called the interstitial cells of Cajal (ICCs). Read on to know more about how this condition develops.

What is a Gastrointestinal Stromal Tumor?

A gastrointestinal stromal tumor (GIST) is a cancer that occurs in the gastrointestinal tract, particularly in the small intestines or stomach area. These tumors stem from the specialized cells called interstitial cells of Cajal (ICCs).

Most commonly found in adults from 40 to 70 years old, the tumor can either be malignant (cancerous) or benign (noncancerous). When the tumor is still small, it may cause little or no signs and symptoms. But some people may report stomach pain, swelling in the abdomen, anorexia, unexplained weight loss, and nausea and vomiting.

In some cases, the tumor may cause bleeding that can lead to anemia or low red blood cell count, fatigue, and weakness. Bleeding in the GI tract can also cause black tarry stools. Bleeding that happens in the stomach can cause vomiting of blood or hematemesis.

What is a GIST Tumor

Cause of Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors (GISTs) are soft-tissue sarcomas found in the digestive system, commonly occurring in the stomach and small intestine. The tumor arises from specialized nerve cells, which are also part of the autonomous nervous system, found in the walls of the gastrointestinal tract.

Usually, a change or mutation in the DNA of one of the cells may lead to the development of GIST. These cells aid in the movement of food through the intestines and control of various digestive processes. The activating mutations of KIT or the platelet-derived growth factor receptor alpha gene (PDGFRA) have been linked to the development of GISTs.

Pathogenesis of Gastrointestinal Stromal Tumor

How does gastrointestinal stromal tumor develop? The possible root cause of GIST is the genetic change in one of several genes. Approximately 80 percent of cases are linked to the mutation in the KIT gene. At the same time, about 10 percent of cases involved mutations in the PDGFRA gene.

What are the KIT and PDGFRA genes? These genes give instructions for creating receptor proteins that are seen in the cell membrane of certain types of cells. They trigger the signaling pathways in the cell. The receptor cells have particular sites where certain proteins, dubbed as ligands, fit into. When the gene receptor protein is switched on, it can lead to the activation of a series of proteins in various signaling pathways. These control numerous cellular processes, including cell division, growth, and survival.

When there are mutations in the PDGFRA and KIT genes, these can cause the proteins to no longer require ligand binding to the stimulated and activated. In turn, the proteins and the signaling pathway is turned on consistently, leading to uncontrolled cell growth, and eventually, GIST development.

Most cases of GIST are not hereditary or passed down in families. GIST has been linked to somatic mutations, which are described as genetic changes that happen only in the tumor cells, in the lifetime of a person, and not because he or she got it from the family. However, in some cases, called familial GISTs, the genetic mutations in the KIT and PDGFRA genes, mutations are passed down through an autosomal dominant pattern.

As a result, gastrointestinal stromal tumors may lead to signs and symptoms, including blood in the vomit or stool, fatigue, abdominal pain, difficulty swallowing, and feeling full even when food consumption is less.

GIST can be treated by surgery, targeted therapy, chemotherapy, and radiotherapy. The prognosis depends on the size and location of the tumor and the stage of the cancer.

Further Reading

Last Updated: Oct 15, 2018

Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.

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