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Endocrine Abstracts (2022) 81 OC6.3 | DOI: 10.1530/endoabs.81.OC6.3

1Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital La Conception, Marseille, France; 2Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer - Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France; 3Service d’Endocrinologie, Centre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, France; 4Endocrinology, Diabetology and Nutrition Unit, University Hospital of Reims, Reims, France; 5Service endocrinologie, CHU de Nancy, hôpital de Brabois, Vandoeuvre-lès-Nancy, France; 6CHU Lille, Service de Biochimie et Biologie moléculaire « Hormonologie, Métabolisme-Nutrition, Oncologie », Lille, France; 7Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France

Context: Mosaicism is a feature of several inherited tumor syndromes but is rarely systematically looked for in routine. MEN1 is an autosomal dominant hereditary syndrome characterized by several endocrine tumors affecting parathyroids, pancreas, and anterior pituitary most of the time, due to inactivating mutations in the MEN1 gene. Few cases of mosaicism in Multiple Endocrine Neoplasia type 1 (MEN1) have been described. MEN1 mosaicism is probably under-diagnosed because it is not routinely investigated. At present, Next generation sequencing (NGS) offers new possibilities to detect mosaicism. The challenge is to distinguish true mosaicism from sequencing artifacts. We reported the first study systematically looking for MEN1 mosaicism in MEN1 suspected patient but without MENI pathogenic variants (PV) at heterozygote state.

Methods: For that, we set up in routine a digital targeted NGS including unique molecular identifiers (UMIs). UMIs are tools for improving molecular detection of rare events in somatic DNA. We established the analytic performance of such method. Next MEN1 mosaicism was then looked for in a cohort of unresolved MEN1 cases addressed in the molecular biology laboratory between 2017 and 2019.

Results: For MEN1, sensitivity was 100% for detecting the variants up to an allelic frequency (AF) of 1%. By using UMIs, false positives were reduced by 98.4% for MEN1. Among a cohort of 119 patients harboring from 2 to 5 MEN1 lesions, we identified 3 patients with MEN1 mosaic PVs. The allelic frequencies ranged from 2.3 to 9.5%. The detection rate of MEN1 mosaicism in patients bearing at least 3 MEN1 lesions was 17% (3/18). No cases are detected in patients with 2 lesions.

Conclusion: we reported here 3 new cases with MEN1 mosaicism. This study deciphered the performances of UMI in MEN1 mosaic diagnosis in routine and underlined that the frequency of mosaicism is probably underestimated in MEN1 suspected patients.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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