Genetic testing considerations for hereditary duodenopancreatic neuroendocrine tumors

MEN1

Germline MEN1, NF1 and VHL variants predisposing to duodenopancreatic neuroendocrine tumours

Duodenopancreatic neuroendocrine tumours (dpNETs) may reveal a hereditary predisposition syndrome (multiple endocrine neoplasia type 1 or 4, von Hippel-Lindau disease, neurofibromatosis type 1, tuberous sclerosis complex), and recent guidelines recommend MEN1 testing in selected patients with an isolated dpNET. This retrospective study analyses genetic and clinical data from 410 tested patients (301 isolated, 109 syndromic dpNETs) for MEN1, NF1, VHL, CDKN1B, TSC1 and TSC2. Thirty-eight patients carried a pathogenic or likely pathogenic variant, most often in MEN1 (n = 27), followed by NF1 (n = 8) and VHL (n = 3), with none in TSC1, TSC2 or CDKN1B. The positive rate reached 29.4% in syndromic dpNETs versus less than 2% in isolated forms. The authors propose limiting extended MEN1 testing in isolated dpNETs to gastrinomas, multiple dpNETs and diagnosis before 40 years of age.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The yield below 2% in isolated dpNETs supports a clinically driven testing strategy, and the three criteria proposed for MEN1 are simple to apply. They remain proposals from a retrospective series rather than validated guidelines, and 38 carriers are not enough to test their sensitivity. The absence of TSC1, TSC2 and CDKN1B variants in a cohort of this size does not rule out these genes.

Analysis by Dr Thibaut Benquey