Early Detection of Relapse by ctDNA Sequencing in a Patient with Metastatic Thymic Tumor and MEN1 Mosaicism - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Endocrinology and Metabolism Year : 2022

Early Detection of Relapse by ctDNA Sequencing in a Patient with Metastatic Thymic Tumor and MEN1 Mosaicism

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Arnaud Lagarde
  • Function : Author
Lauriane Le Collen
  • Function : Author
Camille Boulagnon
  • Function : Author
Hedia Brixi
  • Function : Author
Grégory Mougel
  • Function : Author
Thomas Cuny
Brigitte Delemer
Anne Barlier
  • Function : Author
Pauline Romanet

Abstract

Abstract Context Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by inactivating mutations in the MEN1 gene. In the literature, few cases of MEN1 have been reported because of mosaic MEN1 mutations. Objective We performed an extensive molecular characterization in several lesions and blood samples, including plasmatic circulating cell-free DNA (ccfDNA) in an exceptional case of a patient with MEN1 mosaicism causing primary hyperparathyroidism, multiple pancreatic neuroendocrine tumors (NETs), and a metastatic thymic NET. Methods Blood, ccfDNA and multiple tissue analysis were performed by next-generation sequencing. Results MEN1 mosaicism was confirmed by multiple tissue analysis. Somatic analysis of the largest pancreatic NET revealed the same MEN1 second-hit mutation as found in the thymic lesion, demonstrating its metastatic origin from the thymic lesion. Moreover, in ccfDNA we found the mosaic MEN1 mutation but also the somatic second-hit mutation found in the thymic primary tumor, revealing the presence of circulating tumor DNA (ctDNA). After surgical removal of the pancreatic metastasis, the mutated fraction of both mutations decreased, before increasing again several weeks before a new clinical relapse, suggesting that thymic ctDNA may be used as an early tumor biomarker. Conclusion This exceptional MEN1 case highlighted (1) the importance of looking for MEN1 mosaicism, (2) that MEN1 mosaicism can cause very aggressive disease, and (3) the interest in analyzing ccfDNA for confirming MEN1 mosaicism but also as a potential tumor biomarker for NET.
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Dates and versions

hal-03800311 , version 1 (06-10-2022)

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Arnaud Lagarde, Lauriane Le Collen, Camille Boulagnon, Hedia Brixi, Anne Durlach, et al.. Early Detection of Relapse by ctDNA Sequencing in a Patient with Metastatic Thymic Tumor and MEN1 Mosaicism. Journal of Clinical Endocrinology and Metabolism, 2022, 107 (10), pp.e4154-e4158. ⟨10.1210/clinem/dgac454⟩. ⟨hal-03800311⟩

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