Arnaud Lagarde1, Grégory Mougel1, Lucie Coppin2, Magalie Haissaguerre3, Lauriane Le Collen4,5, Amira Mohamed6, Marc Klein7, Marie-Françoise Odou8,9, Antoine Tabarin3, Hedia Brixi10, Thomas Cuny11, Brigitte Delemer4, Anne Barlier1, Pauline Romanet1. 1. Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital La Conception, Marseille, France. 2. Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer - Heterogeneity Plasticity and Resistance to Therapies, Lille, France. 3. Service d'Endocrinologie, Centre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, France. 4. Endocrinology, Diabetology and Nutrition Unit, University Hospital of Reims, Reims, France. 5. Inserm/CNRS UMR 1283/8199, Pasteur Institute of Lille, EGID, Lille, France. 6. Laboratory of Molecular Biology, Hospital La Conception, APHM, Marseille, France. 7. Service Endocrinologie, CHU de Nancy, Hôpital de Brabois, Vandoeuvre-lès-Nancy, France. 8. CHU Lille, Service de Biochimie et Biologie Moléculaire 'Hormonologie, Métabolisme-Nutrition, Oncologie', Lille, France. 9. Univ. Lille, Inserm, CHU Lille, U1286 - Infinite - Institute for Translational Research in Inflammation, Lille, France. 10. Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France. 11. Aix Marseille Univ, APHM, INSERM, MMG, Department of Endocrinology, Hospital La Conception, Marseille, France.
Abstract
Purpose: Mosaicism is a feature of several inherited tumor syndromes. Only a few cases of mosaicism have been described in multiple endocrine neoplasia type 1 (MEN1). Next-generation sequencing (NGS) offers new possibilities for detecting mosaicism. Here, we report the first study to systematically look for MEN1 mosaicism, using blood DNA, in MEN1-suspected patients but without MEN1 pathogenic variants (PV) in a heterozygous state. Methods: Digital targeted NGS, including unique molecular identifiers (UMIs), was performed in routine practice, and the analytic performance of this method was verified. Results: Among a cohort of 119 patients harboring from 2 to 5 MEN1 lesions, we identified 3 patients with MEN1 mosaic PVs. The allele 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 were detected in patients with two lesions. Conclusion: We report here three new cases with MEN1 mosaicism. This study examined the performance of UMI in the diagnosis of MEN1 mosaicism in routine practice, and our results underline that the frequency of mosaicism is probably underestimated in patients with suspected MEN1.
Purpose: Mosaicism is a feature of several inherited tumor syndromes. Only a few cases of mosaicism have been described in multiple endocrine neoplasia type 1 (MEN1). Next-generation sequencing (NGS) offers new possibilities for detecting mosaicism. Here, we report the first study to systematically look for MEN1 mosaicism, using blood DNA, in MEN1-suspected patients but without MEN1 pathogenic variants (PV) in a heterozygous state. Methods: Digital targeted NGS, including unique molecular identifiers (UMIs), was performed in routine practice, and the analytic performance of this method was verified. Results: Among a cohort of 119 patients harboring from 2 to 5 MEN1 lesions, we identified 3 patients with MEN1 mosaic PVs. The allele 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 were detected in patients with two lesions. Conclusion: We report here three new cases with MEN1 mosaicism. This study examined the performance of UMI in the diagnosis of MEN1 mosaicism in routine practice, and our results underline that the frequency of mosaicism is probably underestimated in patients with suspected MEN1.
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