Endocrine Abstracts

Hereditary genetic variants are common among patients with endocrine tumours. Some specific clinical conditions are informative for certain monogenic syndromes (i.e., Carney complex, MEN1, MEN2, von Hippel Lindau syndrome) but manifestations characteristic for these syndromes occur more commonly as apparently sporadic. Other tumours, i.e., pheochromocytoma/paragangliomas (PPGL) are linked to multiple genes, hence a multigene approach in molecular genetic testing strategy is recommended. As a national reference centre for molecular genetic testing of patients with hereditary cancer, we prospectively tested a multigene panel’s diagnostic utility which covers 113 genes associated with various tumours. The most common genes responsible for hereditary endocrine tumours are also included in this panel. Between October 2021 and December 2022, we analysed 97 patients as part of their routine clinical and molecular genetic diagnostic workup. All pathogenic/likely pathogenic variants with unknown significance were validated from a second DNA sample using gold-standard Sanger sequencing or multiplex ligation-dependent probe amplification. Patients with primary hyperparathyroidism, gastro-pancreatic neuroendocrine tumours, pheochromocytoma, paraganglioma, adrenocortical cancer, medullary thyroid cancer, neurofibromatosis, etc. were referred for testing. Of 97 patients, in 24 cases the relevant P/lP variants were identified (24/97; 25%). Of these, the most common variants were detected in MEN1, SDHx, and NF1 genes. In 8 cases secondary findings were reported in BRCA2, ATM, CHEK2, MSH6 and NF1 genes (8/96; 8%). Our data show that using a comprehensive multigene panel as a routine diagnostic tool for testing patients with endocrine tumours yields a high diagnostic benefit in a short turnaround time. Incidentally identified variants may serve as a potential therapeutic target (such as BRCA2 or MSH6) in tumours where therapeutic possibilities are limited (i.e., adrenocortical cancer).