PMID- 29725435
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 15
IP  - 5
DP  - 2018 May
TI  - Uncovering the heterogeneous genetic variations in two insulin-expressing tumors 
      in a patient with MEN1.
PG  - 7123-7131
LID - 10.3892/ol.2018.8184 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is associated with a heterozygous 
      inherited mutation of the menin 1 (MEN1) gene; however, the molecular 
      pathogenesis remains to be fully elucidated. In the present study, whole exome 
      sequencing was performed on two pancreatic neuroendocrine tumors (PNETs), termed 
      T1 and T2, peri-tumoral tissue (PT) and a blood sample obtained from a patient 
      with MEN1. The cells in T1 and T2, but not PT, showed loss of chromosome 11 where 
      MEN1 was located, confirming that the loss of heterozygosity (LOH) of MEN1 was a 
      crucial event in tumorigenesis. PT exhibited chromosome copy number variations 
      (CNVs), suggesting that CNVs may occur ahead of MEN1-associated tumorigenesis. 
      The ploidy, CNVs and somatic point mutations were completely different in T1 and 
      T2, showing the first evidence that multiple PNETs in patients with MEN1 are 
      heterogeneous and arise from polyclonal origins. With the except of one recurrent 
      and possibly benign mutation, no other suspicious driver mutations were 
      identified in the tumors. By contrast, accompanying several chromosome losses, 
      germline heterozygous mutations in the tumor suppressor genes, mucin 6, 
      oligomeric mucus/gel-forming (MUC6), and G protein-coupled receptor 17 (GPR17) 
      showed loss of heterozygosity in the two tumors, or in T2, respectively. These 
      data demonstrated that chromosome instability may aggravate inherited mutations 
      other than MEN1, thus contributing to the tumorigenesis in MEN1-associated PNETs.
FAU - Wang, Zai
AU  - Wang Z
AD  - Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 
      100029, P.R. China.
FAU - Liu, Liguo
AU  - Liu L
AD  - Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, 
      P.R. China.
FAU - Luo, Jie
AU  - Luo J
AD  - Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, P.R. 
      China.
FAU - Guo, Jing
AU  - Guo J
AD  - Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 
      100029, P.R. China.
FAU - Zhai, Min
AU  - Zhai M
AD  - Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 
      100029, P.R. China.
FAU - Zhang, Wenjian
AU  - Zhang W
AD  - Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 
      100029, P.R. China.
FAU - Yang, Zhiying
AU  - Yang Z
AD  - Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180306
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC5920406
OTO - NOTNLM
OT  - insulin
OT  - multiple endocrine neoplasia type 1
OT  - pancreatic neuroendocrine tumor
OT  - whole exome sequencing
EDAT- 2018/05/05 06:00
MHDA- 2018/05/05 06:01
PMCR- 2018/03/06
CRDT- 2018/05/05 06:00
PHST- 2017/09/22 00:00 [received]
PHST- 2018/01/29 00:00 [accepted]
PHST- 2018/05/05 06:00 [entrez]
PHST- 2018/05/05 06:00 [pubmed]
PHST- 2018/05/05 06:01 [medline]
PHST- 2018/03/06 00:00 [pmc-release]
AID - OL-0-0-8184 [pii]
AID - 10.3892/ol.2018.8184 [doi]
PST - ppublish
SO  - Oncol Lett. 2018 May;15(5):7123-7131. doi: 10.3892/ol.2018.8184. Epub 2018 Mar 6.