Gastrointestinal Stromal tumours and the KIT and PDGFRA genes

Gastrointestinal stromal tumours (GIST) and the KIT and PDGFRA genes

Gastrointestinal stromal tumours (GIST) are abnormal growths (tumours) that arise in the supporting tissue (stroma). GIST occur mainly in the stomach and small intestine but can occur anywhere in the gastrointestinal tract.

GIST are rare tumours affecting less than 1: 20,0000 people each year. Familial GIST is even more rare, affecting less than 100 families world wide.

The genes KIT and PDGFRA are commonly damaged in sporadic GIST. This is called a "somatic" mutation. In these cases, the mutation occurred in the GIST as it grew. While somatic mutations of this kind are almost never passed on, they can be targeted by cancer therapies.

Familial GIST can be caused by germline (inheritable) mutations in genes such as KIT and PDGFRA.

Another somatic test called immunohistochemical testing (IHC) can be performed on the GIST to see if it occurred due to an inherited mutation in a different group of genes, the SDH genes. The IHC staining test looks for the presence of the SDHA and SHDB proteins. If the proteins are missing, it may be because of germline (inherited) mutation (pathogenic variant) in one of the SDH genes.

Germline SDH mutations are associated with Hereditary Paraganglioma and Pheochromocytoma syndrome. GISTs occurring along with paraganglioma was described clinically as the Carney-Stratakis dyad. It's an old term and no longer used. Read more about Hereditary Paraganglioma and Pheochromocytoma syndrome.

Perhaps surprisingly, familial GISTs are more likely to be slow growing and less like to spread to other parts of the body (metastasise)

There is a 50% chance of a person who carries a germline KIT, PDGFRA or SDH mutation, whether male or female, passing the mutation to their son or daughter. If a mutation is identified, then predictive testing is available for blood relatives.

Does this sound like you or your family? Has a germline KIT, PDGFRA or SDH mutation been detected in a blood relative? Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed.

These links may be useful