PMID- 36112497
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231105
IS  - 2049-3614 (Print)
IS  - 2049-3614 (Electronic)
IS  - 2049-3614 (Linking)
VI  - 11
IP  - 11
DP  - 2022 Nov 1
TI  - Systematic detection of mosaicism by using digital NGS reveals three new MEN1 
      mosaicisms.
LID - e220093 [pii]
LID - 10.1530/EC-22-0093 [doi]
AB  - 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.
FAU - Lagarde, Arnaud
AU  - Lagarde A
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
FAU - Mougel, Gregory
AU  - Mougel G
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
FAU - Coppin, Lucie
AU  - Coppin L
AD  - Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer - 
      Heterogeneity Plasticity and Resistance to Therapies, Lille, France.
FAU - Haissaguerre, Magalie
AU  - Haissaguerre M
AD  - Service d'Endocrinologie, Centre Hospitalier Universitaire, Hopital du Haut 
      Leveque, Pessac, France.
FAU - Le Collen, Lauriane
AU  - Le Collen L
AD  - Endocrinology, Diabetology and Nutrition Unit, University Hospital of Reims, 
      Reims, France.
AD  - Inserm/CNRS UMR 1283/8199, Pasteur Institute of Lille, EGID, Lille, France.
FAU - Mohamed, Amira
AU  - Mohamed A
AD  - Laboratory of Molecular Biology, Hospital La Conception, APHM, Marseille, France.
FAU - Klein, Marc
AU  - Klein M
AD  - Service Endocrinologie, CHU de Nancy, Hopital de Brabois, Vandoeuvre-les-Nancy, 
      France.
FAU - Odou, Marie-Francoise
AU  - Odou MF
AUID- ORCID: 0000-0002-6120-1098
AD  - CHU Lille, Service de Biochimie et Biologie Moleculaire 'Hormonologie, 
      Metabolisme-Nutrition, Oncologie', Lille, France.
AD  - Univ. Lille, Inserm, CHU Lille, U1286 - Infinite - Institute for Translational 
      Research in Inflammation, Lille, France.
FAU - Tabarin, Antoine
AU  - Tabarin A
AD  - Service d'Endocrinologie, Centre Hospitalier Universitaire, Hopital du Haut 
      Leveque, Pessac, France.
FAU - Brixi, Hedia
AU  - Brixi H
AD  - Department of Gastroenterology and Digestive Oncology, Reims University Hospital, 
      Reims, France.
FAU - Cuny, Thomas
AU  - Cuny T
AUID- ORCID: 0000-0002-8440-0030
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Department of Endocrinology, Hospital La 
      Conception, Marseille, France.
FAU - Delemer, Brigitte
AU  - Delemer B
AD  - Endocrinology, Diabetology and Nutrition Unit, University Hospital of Reims, 
      Reims, France.
FAU - Barlier, Anne
AU  - Barlier A
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
FAU - Romanet, Pauline
AU  - Romanet P
AUID- ORCID: 0000-0003-1775-9569
AD  - Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital 
      La Conception, Marseille, France.
LA  - eng
PT  - Journal Article
DEP - 20221014
PL  - England
TA  - Endocr Connect
JT  - Endocrine connections
JID - 101598413
PMC - PMC9578105
OTO - NOTNLM
OT  - MEN1
OT  - NGS
OT  - de novo
OT  - deep-sequencing
OT  - digital NGS
OT  - hyperparathyroidism
OT  - mosaic
OT  - mosaicism
OT  - pancreatic neuroendocrine tumor
OT  - pituitary adenoma
OT  - thymic tumor
OT  - unique molecular identifier
EDAT- 2022/09/17 06:00
MHDA- 2022/09/17 06:01
PMCR- 2022/10/14
CRDT- 2022/09/16 12:32
PHST- 2022/09/02 00:00 [received]
PHST- 2022/09/16 00:00 [accepted]
PHST- 2022/09/17 06:00 [pubmed]
PHST- 2022/09/17 06:01 [medline]
PHST- 2022/09/16 12:32 [entrez]
PHST- 2022/10/14 00:00 [pmc-release]
AID - e220093 [pii]
AID - EC-22-0093 [pii]
AID - 10.1530/EC-22-0093 [doi]
PST - epublish
SO  - Endocr Connect. 2022 Oct 14;11(11):e220093. doi: 10.1530/EC-22-0093. Print 2022 
      Nov 1.