PMID- 28503312
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2054-345X (Print)
IS  - 2054-345X (Electronic)
IS  - 2054-345X (Linking)
VI  - 4
DP  - 2017
TI  - Germline and somatic genetic changes in multicentric tumors obtained from a 
      patient with multiple endocrine neoplasia type 1.
PG  - 17013
LID - 10.1038/hgv.2017.13 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused 
      by germline mutations of the MEN1 gene located in chromosome 11q13. In patients 
      with MEN1, multicentric tumors develop in the involved organs; however, precise 
      evaluation of genetic changes in these multicentric tumors has not been 
      performed. In the present study, using whole-exome sequencing, we analyzed 
      germline and somatic genetic changes in blood cells, two pancreatic endocrine 
      tumors and one duodenal tumor obtained from a patient with MEN1 gastrinoma. We 
      found that this patient possessed a novel germline mutation of the MEN1 gene 
      [NM_137099.2:c.1505dupA (p.Lys502Lysfs); the localization was Chr11:64572134 on 
      Assembly GRCh37], in which an adenine insertion in codon 502 of the MEN1 gene 
      resulted in a frame shift and a premature stop codon. In terms of heterozygosity, 
      the mutated allele was heterozygous in blood cells, hemizygous in the two 
      pancreatic tumors and homozygous in the duodenal tumor. Immunohistochemical 
      staining confirmed that only truncated menin protein accumulated in the nucleus 
      of the tumor tissues. Further evaluation of tumor-specific somatic mutations in 
      two pancreatic tumors did not detect single-nucleotide variations (SNVs) in 609 
      cancer-associated genes designated by the COSMIC cancer gene census, suggesting 
      that the germline MEN1 mutation and resultant loss of heterozygosity played a 
      major role in tumorigenesis. In the duodenal tumor, in addition to the germline 
      MEN1 mutation, single-nucleotide variations in two cancer-associated genes were 
      found. Further studies are required to clarify the role of these somatic 
      single-nucleotide variations in the progression of MEN1 tumors.
FAU - Naruoka, Akane
AU  - Naruoka A
AD  - Drug Discovery and Development Division, Shizuoka Cancer Center Research 
      Institute, Shizuoka, Japan.
FAU - Ohnami, Sumiko
AU  - Ohnami S
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka, Japan.
FAU - Nagashima, Takeshi
AU  - Nagashima T
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka, Japan.
AD  - SRL Inc., Tokyo, Japan.
FAU - Serizawa, Masakuni
AU  - Serizawa M
AD  - Drug Discovery and Development Division, Shizuoka Cancer Center Research 
      Institute, Shizuoka, Japan.
FAU - Ohshima, Keiichi
AU  - Ohshima K
AD  - Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, 
      Japan.
FAU - Ohnami, Shumpei
AU  - Ohnami S
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka, Japan.
FAU - Urakami, Kenichi
AU  - Urakami K
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka, Japan.
FAU - Horiuchi, Yasue
AU  - Horiuchi Y
AD  - Division of Genetic Counseling, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
FAU - Kiyozumi, Yoshimi
AU  - Kiyozumi Y
AD  - Division of Genetic Counseling, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
FAU - Abe, Masato
AU  - Abe M
AD  - Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
FAU - Nakajima, Takashi
AU  - Nakajima T
AD  - Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
FAU - Sugiura, Teiichi
AU  - Sugiura T
AD  - Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 
      Shizuoka, Japan.
FAU - Uesaka, Katsuhiko
AU  - Uesaka K
AD  - Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 
      Shizuoka, Japan.
FAU - Kusuhara, Masatoshi
AU  - Kusuhara M
AD  - Drug Discovery and Development Division, Shizuoka Cancer Center Research 
      Institute, Shizuoka, Japan.
AD  - Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, 
      Japan.
FAU - Yamaguchi, Ken
AU  - Yamaguchi K
AD  - Shizuoka Cancer Center, Shizuoka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170427
PL  - England
TA  - Hum Genome Var
JT  - Human genome variation
JID - 101652445
PMC - PMC5406389
COIS- The authors declare no conflict of interest.
EDAT- 2017/05/16 06:00
MHDA- 2017/05/16 06:01
PMCR- 2017/04/27
CRDT- 2017/05/16 06:00
PHST- 2016/09/09 00:00 [received]
PHST- 2017/02/12 00:00 [revised]
PHST- 2017/02/23 00:00 [accepted]
PHST- 2017/05/16 06:00 [entrez]
PHST- 2017/05/16 06:00 [pubmed]
PHST- 2017/05/16 06:01 [medline]
PHST- 2017/04/27 00:00 [pmc-release]
AID - hgv201713 [pii]
AID - 10.1038/hgv.2017.13 [doi]
PST - epublish
SO  - Hum Genome Var. 2017 Apr 27;4:17013. doi: 10.1038/hgv.2017.13. eCollection 2017.