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.
Genetic Testing With Other Possible NETs
We also recommend genetic testing any time we suspect a rare NET called a gastrinoma, especially if you have a family history of it.
With other suspected pancreatic and GI NETs, we recommend genetic testing in more limited circumstances. We take the same approach for lung NETs. Factors we take into account include:
- Family history of a known genetic variant
- Location of tumor
- Hormone release
- Aggressive tumor behavior
- Additional signs of a syndrome — either other cancer types or non-cancer conditions
- NETs initially forming in more than one spot
How Genetic Mutations Such as SDHB Affect NET Care
Identifying inherited genetic variants tied to neuroendocrine tumors is important for several reasons:
- Monitoring: If you haven’t developed a NET, we can create an individualized plan with imaging and blood work to watch for tumors. Earlier diagnosis provides a better chance at effective treatment. We can also test family members and make plans for anyone who tests positive. In some cases, we may recommend rapid, full-body MRI — an approach we developed.
- Treatment: When NETs do form, some variants tend to cause more aggressive disease. By knowing which variant is at play, we can adjust treatment recommendations.
- Support for family members: If you carry an inherited variant associated with an increased risk of NETs, your family members may also carry that change. Testing family members can improve their quality of life, as we can watch for tumors and reduce the risk of severe disease.
It’s important to keep in mind that if a parent has a known variant, you only have a 50-50 chance of inheriting it. Even if you do have that variant, you will not necessarily develop a NET. With some variants, the risk of developing disease remains relatively low. For others like MEN1, the risk is as high as 90 percent.
Why Choose the Abramson Cancer Center 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 team and 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.
Request an Appointment
To make an appointment, please call 800-789-7366 or request a callback.