PMID- 35904487
OWN - NLM
STAT- MEDLINE
DCOM- 20220929
LR  - 20221012
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 107
IP  - 10
DP  - 2022 Sep 28
TI  - Early Detection of Relapse by ctDNA Sequencing in a Patient with Metastatic 
      Thymic Tumor and MEN1 Mosaicism.
PG  - e4154-e4158
LID - 10.1210/clinem/dgac454 [doi]
AB  - 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.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Lagarde, Arnaud
AU  - Lagarde A
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception Laboratory of 
      Molecular Biology, Marseille, France.
FAU - Le Collen, Lauriane
AU  - Le Collen L
AD  - Department of Endocrinology Diabetology, University of Reims , Reims, France.
AD  - Inserm/CNRS UMR 1283/8199, Institut Pasteur de Lille , EGID, Lille, France.
AD  - Department of Clinical Genetics, University of Reims , Reims, France.
FAU - Boulagnon, Camille
AU  - Boulagnon C
AD  - Biopathology Laboratory, Pole de Biologie Territorial, CHU de Reims, 51092 Reims, 
      France.
AD  - Universite de Reims Champagne Ardenne (URCA), CNRS, UMR 7369 MEDyC, Reims, 
      France.
FAU - Brixi, Hedia
AU  - Brixi H
AD  - Department of Gastroenterology and Digestive Oncology, Reims University Hospital, 
      Reims, France.
FAU - Durlach, Anne
AU  - Durlach A
AD  - Biopathology Laboratory, Pole de Biologie Territorial, CHU de Reims, 51092 Reims, 
      France.
AD  - Inserm UMR-S 1250, 51092 Reims, France.
FAU - Mougel, Gregory
AU  - Mougel G
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception Laboratory of 
      Molecular Biology, Marseille, France.
FAU - Cuny, Thomas
AU  - Cuny T
AUID- ORCID: 0000-0002-8440-0030
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception Department of 
      endocrinology, Marseille, France.
FAU - Delemer, Brigitte
AU  - Delemer B
AUID- ORCID: 0000-0002-4320-2601
AD  - Department of Endocrinology Diabetology, University of Reims , Reims, France.
FAU - Barlier, Anne
AU  - Barlier A
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception Laboratory of 
      Molecular Biology, Marseille, France.
FAU - Romanet, Pauline
AU  - Romanet P
AUID- ORCID: 0000-0003-1775-9569
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception Laboratory of 
      Molecular Biology, Marseille, France.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Circulating Tumor DNA)
RN  - Thymoma, Familial
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - *Circulating Tumor DNA
MH  - Humans
MH  - Mosaicism
MH  - *Multiple Endocrine Neoplasia Type 1/genetics/pathology
MH  - Neoplasm Recurrence, Local
MH  - *Neoplasms, Second Primary
MH  - Thymoma
MH  - *Thymus Neoplasms/diagnosis/genetics/surgery
OTO - NOTNLM
OT  - biomarker
OT  - ccfDNA
OT  - circulating cell-free DNA
OT  - circulating tumor DNA
OT  - genetic counselling
OT  - mosaic mutation
OT  - thymic neuroendocrine tumor
EDAT- 2022/07/30 06:00
MHDA- 2022/09/30 06:00
CRDT- 2022/07/29 10:33
PHST- 2022/04/28 00:00 [received]
PHST- 2022/07/30 06:00 [pubmed]
PHST- 2022/09/30 06:00 [medline]
PHST- 2022/07/29 10:33 [entrez]
AID - 6651815 [pii]
AID - 10.1210/clinem/dgac454 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4154-e4158. doi: 
      10.1210/clinem/dgac454.