Cardiovascular

Genetic testing considerations for hereditary duodenopancreatic neuroendocrine tumors.

Charnay T, Giannetti C, et al. • Journal of neuroendocrinology • 2026

TL;DR

MEN1 is the predominant gene underlying predisposition to dpNETs, and the low diagnostic yield in isolated dpNETs supports a clinically stratified genetic testing strategy.

Key Findings

Results

In a retrospective cohort of 410 patients tested for duodenopancreatic neuroendocrine tumors, 38 carried a (likely) pathogenic variant, with MEN1 the most common.

410 patients were included: 301 with isolated (non-syndromic) dpNETs and 109 with syndromic dpNETs.
Of the 38 (L)PV carriers, 27 had MEN1 variants, 8 had NF1 variants and 3 had VHL variants.
Genes assessed were MEN1, NF1, VHL, CDKN1B, TSC1 and TSC2.

Results

No (L)PVs were found in TSC1, TSC2, or CDKN1B in this cohort.

These genes were analyzed along with MEN1, NF1 and VHL.
No TSC1, TSC2, or CDKN1B (L)PVs were detected among the 410 patients.

Results

Patients with syndromic dpNETs had a much higher genetic positivity rate than those with isolated dpNETs.

The positive rate was 29.4% in syndromic dpNETs versus under 2% in isolated dpNETs.
The cohort included 109 syndromic and 301 isolated dpNET patients.

Conclusions

The low diagnostic yield in isolated dpNETs supports a clinically stratified approach to genetic testing.

Clinical evaluation should systematically assess signs of MEN1, MEN4, VHL, NF1 or TSC to guide which genetic testing is performed.
This approach is intended to maximize diagnostic yield.

Conclusions

For MEN1, the authors propose limiting extended genetic testing in patients with isolated dpNETs to specific clinical criteria.

Proposed criteria: (i) gastrinoma, (ii) multiple dpNETs, or (iii) diagnosis before 40 years of age.
This is a proposal in the context of recent guidelines recommending MEN1 testing in selected patients with an isolated dpNET.

What This Means

This study looked back at genetic test results from 410 people with neuroendocrine tumors of the duodenum or pancreas. Some of these tumors are caused by inherited syndromes, such as MEN1, VHL disease, neurofibromatosis type 1 and tuberous sclerosis. The researchers wanted to know how often genetic testing finds an inherited cause, and whether testing should go beyond MEN1 for people whose only finding is a tumor of this kind. Overall, 38 patients had a disease-causing or likely disease-causing variant. Most were in MEN1 (27), followed by NF1 (8) and VHL (3). None were found in TSC1, TSC2 or CDKN1B. Among patients whose tumors came with other signs of a syndrome, about 29% had a variant. Among those with an isolated tumor, fewer than 2% did. This research suggests that testing is most useful when guided by a careful clinical exam for signs of these syndromes, rather than applied broadly to everyone with an isolated tumor. For MEN1, the authors propose that wider testing in isolated cases be limited to people with a gastrinoma, multiple tumors, or a diagnosis before age 40. Because the study was retrospective, these suggestions would need confirmation in further work.

Have a question about this study?

Citation

Charnay T, Giannetti C, Sahakian N, Haissaguerre M, Oziel-Taieb S, Mari V, et al.. (2026). Genetic testing considerations for hereditary duodenopancreatic neuroendocrine tumors.. Journal of neuroendocrinology. https://doi.org/10.1111/jne.70305

Key Findings

What This Means

Have a question about this study?

Related Research

Citation