The prevalence of germline variants is high in Japanese patients with paraganglioma and pheochromocytoma

Certain types of tumors can be passed down from one generation to another. It is crucial to determine the cause of these tumors to treat them. However, most studies have been conducted on Caucasian patients. A research group from the University of Tsukuba has now conducted the first study of two types of inherited cancer in Japanese patients. They have found that the frequency of genetic variation is similar to that of European patients.

Certain types of tumors have a single genetic variant for their cause, whereas others can result from many genetic changes, referred to as genetic heterogeneity. The two most prevalent types of tumors inherited with genetic heterogeneity are both cancers of chromaffin cells. which is a particular type of cell that can receive signals from the nervous system and release hormones. These tumors can be found in the adrenal gland (where they’re called a pheochromocytoma), or in the regions of the body that regulate blood pressure (where it’s called paraganglioma). Although they develop in different places, the two tumors have a common underlying pathology and genetic background and so are grouped together as pheochromocytoma/paraganglioma (PPGL).

Seven major genes have been identified as “susceptibility genes” for PPGL, that is, genes in which mutations could lead to an increased risk of developing tumors. The team looked at 370 cases of PPGL and 327 were found to not have a family history, which is known as “apparently sporadic” cases. The researchers have identified seven susceptibility genes based on blood samples and clinical information.

Nearly a quarter of the cases of sporadic the PPGL syndrome were found to have some genetic variation in at least one gene.

Dr. Masato Yonamine, lead author

One of the genes, known as SDHB was mutated the most frequently, and showed an connection with metastatic tumors that spread to other parts of the body. The team also discovered nine genetic variants that were previously unknown.

“The results of our study will provide the necessary information to allow the PPGL genetic test to be covered by insurance companies in Japan,” says senior author Professor Kazuhiro Takekoshi.

This work underscores the importance of conducting genetic testing when cases of PPGL are detected in Japan not just to determine the most appropriate treatment plan for the patient, but also to screen other family members who may have genetic variants and are therefore at risk of developing PPGL.