Endocrine Abstracts

Objective: Next Generation Sequencing technique (NGS) allows the analysis of a whole set of genes in the same time. It is, now, used, in our laboratory for the genetic screening of neuroendocrine tumors associated with Multiple Endocrine neoplasia type 1(MEN1)The objective of the present study was to assess the efficiency of this approach and the relevance of the results regarding the current genetic screening recommendations.

Methods: The data of all patients tested by NGS during the last 3 years forneuroendocrine tumors associated with MEN1 were collected. NGS technique allowed the analysis of the coding sequence and the intronic bounds of 13 genes in a total of 583 patients.

Results: Genetic variants were identified in 53 patients: 30 of them were located in the MEN 1 gene, 5 in CDKN1B et 6 in a gene involved in familial hypocalciuric hypercalcema 38 were classified as pathogenic or probably pathogenic variants and 15 were classified as variant of undetermined signification. Most of patients with more than one neuroendocrine tumor did not carry any mutation. Statistical analysis identified three main predictors of positive genetic testing: male gender, age less than 50 years old at diagnosis, and having more than one type of endocrine tumor.

Conclusion: In this study, a genetic variant has been identified by NGS in 10% of cases with predictive factors of positive genetic testing in accordance with current guidelines. This suggests that NGS approach is a reliable technique for the genetic screening of patients with neuroendocrine tumors. However, other approaches remain necessary to identify more mutations. Variants interpretation remains a major problem which needs a close collaboration between laboratories and clinicians and the improvement of new effective tools.