Genetic testing for neuroendocrine tumor risk

The NETs team at Penn Medicine provides the latest genetic testing, with leading expertise to interpret results and apply them to your personalized care. As part of this process, we offer genetic counseling to help you understand what it all means for you and your family.

The genetic testing we provide for NETs is referred to as germline (inherited) genetic testing, meaning that it examines cells present since birth.

Are neuroendocrine tumors hereditary?

Most of the time, we don’t know why neuroendocrine tumors form. Sometimes, though, a NET develops because of a genetic mutation (also known as a variant) inherited from a parent. Overall, these hereditary tumors represent a small share of NETs — just 10 percent. But among people with pheochromocytomas and paragangliomas the proportion jumps to 40 percent.

Genes with mutations tied to particular NETs include:

  • EPAS1, also called HIF2A: paragangliomas
  • FH: pheochromocytomas, paragangliomas
  • MAX: pheochromocytomas
  • MEN1: gastrointestinal (GI) NETs, lung NETs, pancreatic NETs
  • NF1: pheochromocytomas
  • RET: pheochromocytomas
  • SDHA, SDHAF2, SDHB, SDHC and SDHD (group of related genes): paragangliomas
  • TMEM127: pheochromocytomas
  • VHL: GI NETs, pancreatic NETs, pheochromocytomas

Changes in some of these genes are tied to syndromes, meaning they can cause more than one disease across a person’s lifetime, including certain NETs. These syndromes include:

  • Hereditary paraganglioma and pheochromocytoma: People with this syndrome develop at least one pheochromocytoma or paraganglioma, and sometimes more. It’s caused by a mutation in a SDHAF2, SDHB, SDHC or SDHD gene.
  • Multiple endocrine neoplasia type 1 (MEN1): This syndrome can cause a number of tumors, including pancreatic NETs. It’s caused by a mutation in the MEN1 gene.
  • Multiple endocrine neoplasia type 2 (MEN2): People with this condition can develop a number of tumors, including pheochromocytoma. It’s caused by a mutation in the RET gene.
  • Von Hippel-Lindau (VHL) syndrome: In addition to pancreatic NETs and pheochromocytomas, this syndrome can cause a range of tumors and other effects. It’s tied to a mutation in the VHL gene.

Learn more about multiple endocrine neoplasia and von Hippel-Lindau syndrome.

Looking for hereditary paragangliomas and hereditary pheochromocytomas

We recommend genetic testing for all people with pheochromocytomas or paragangliomas. Given the high rates of underlying hereditary disease, such testing is considered standard of care.

Why choose Penn Medicine for NET genetic support?

We have years of experience working with the genetic aspects of neuroendocrine tumors. We were one of the first programs in the country to offer genetic testing. When national guidelines were recently updated to test all people with pheochromocytomas and paragangliomas, we had already been doing so for many years.

When you come to our program, you’ll find:

  • Expertise: Our doctors publish leading papers on NET genetics and give national talks. We have a particular focus on von Hippel-Lindau disease (VHL), for which we are designated a Comprehensive Clinical Care Center by the VHL Alliance. Our team also conducts research into NET genetics, such as why some variants are more likely to cause tumors than others. Learn more about our neuroendocrine tumor research.
  • Help for all ages: Although inherited variants usually don’t cause NETS until adulthood, these tumors can occasionally show up in children. We work with people of all ages. We also partner with the Children’s Hospital of Philadelphia (CHOP) to transition children to our care when it’s time.
  • Thorough consultations: In addition to discussing testing and interpreting results, we can help you with issues such as family planning. We also have a genetics expert at our weekly tumor board, where cases get discussed and we determine what care to recommend.
  • Family support: When we find an inherited genetic change tied to NETs, we help provide information to family members. If they decide to pursue genetic testing, they can do so through our program. We can also help them find testing and counseling closer to home.
National Cancer Institute "Designated Comprehensive Cancer Center" badge on top of exterior shot of the Perelman Center for Advanced Medicine

Rated “exceptional” by The National Cancer Institute

Penn Medicine’s Abramson Cancer Center is a world leader in cancer research, patient care, and education. Our status as a national leader in cancer care is reflected in our continuous designation as a Comprehensive Cancer Center by the National Cancer Institute (NCI) since 1973, one of 7 such centers in the United States. The ACC is also a member of the National Comprehensive Cancer Network, one of a select few cancer centers in the U.S., that are working to promote equitable access to high-quality, advanced cancer care.

Schedule an appointment

We can help you schedule an appointment or you can search our directory of specialists.