PMID- 28969599
OWN - NLM
STAT- MEDLINE
DCOM- 20171013
LR  - 20181113
IS  - 1471-2350 (Electronic)
IS  - 1471-2350 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Oct 2
TI  - Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple 
      endocrine neoplasia type 1 using whole-exome sequencing.
PG  - 106
LID - 10.1186/s12881-017-0465-9 [doi]
LID - 106
AB  - BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal 
      dominant hereditary disorder characterized by the presence of endocrine tumors 
      affecting the parathyroid, pancreas, and pituitary. A heterozygous germline 
      inactivating mutation in the MEN1 gene (first hit) may be followed by somatic 
      loss of the remaining normal copy or somatic mutations in the MEN1 gene (second 
      hit). Whole-exome sequencing has been successfully used to elucidate the 
      mutations associated with the different types of tumors. CASE PRESENTATION: We 
      performed whole-exome sequencing (WES) on three parathyroid tumors, one 
      pancreatic insulinoma, and a blood sample taken from the same patient with MEN1 
      to study tumor heterogeneity in MEN1 originating from different tumors. We 
      identified a novel frame-shift deletion (c.1382_1383delAG, p.E461GfsX69) in the 
      MEN1 gene using WES, which was confirmed by Sanger sequencing. WES and the SNP 
      array revealed somatic LOH on chromosome 11 in parathyroid tumors (left upper, 
      left lower, and right upper parathyroid). However, we did not detect a somatic 
      MEN1 gene mutation or LOH in the pancreatic insulinoma. WES revealed two somatic 
      functional variants outside the MEN1 gene in the pancreatic insulinoma. 
      CONCLUSIONS: This study revealed heterogeneity among tumors in the same patient 
      with MEN1, suggesting that different tumor-specific tumorigenic mechanisms may 
      contribute to the pathogenesis of MEN1 tumors. The present study supports the 
      clinical applicability of the WES strategy to research on multiple tumor samples 
      and blood.
FAU - Kim, Bo-Young
AU  - Kim BY
AD  - Division of Intractable Diseases, Center for Biomedical Sciences, Korea National 
      Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 
      28159, South Korea.
FAU - Park, Mi-Hyun
AU  - Park MH
AD  - Division of Intractable Diseases, Center for Biomedical Sciences, Korea National 
      Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 
      28159, South Korea.
FAU - Woo, Hae-Mi
AU  - Woo HM
AD  - Division of Intractable Diseases, Center for Biomedical Sciences, Korea National 
      Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 
      28159, South Korea.
FAU - Jo, Hye-Yeong
AU  - Jo HY
AD  - Division of Intractable Diseases, Center for Biomedical Sciences, Korea National 
      Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 
      28159, South Korea.
FAU - Kim, Ji Hoon
AU  - Kim JH
AD  - Department of Surgery, Eulji University Hospital, Daejeon, South Korea.
FAU - Choi, Hyung Jin
AU  - Choi HJ
AD  - Department of Anatomy, Department of Biomedical Science, Neuroscience Research 
      Institute, Seoul National University College of Medicine, 28 Yongon-dong, 
      Chongno-gu, Seoul, South Korea. hjchoi@snu.ac.kr.
FAU - Koo, Soo Kyung
AU  - Koo SK
AUID- ORCID: 0000-0002-2133-3088
AD  - Division of Intractable Diseases, Center for Biomedical Sciences, Korea National 
      Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 
      28159, South Korea. skkoo@nih.go.kr.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171002
PL  - England
TA  - BMC Med Genet
JT  - BMC medical genetics
JID - 100968552
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Exome/genetics
MH  - Genetic Testing/*methods
MH  - Germ-Line Mutation
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Humans
MH  - Insulinoma/*genetics
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Pancreatic Neoplasms/complications/*genetics
MH  - Parathyroid Neoplasms/complications/*genetics
MH  - Pedigree
MH  - Proto-Oncogene Proteins/genetics
PMC - PMC5625714
OTO - NOTNLM
OT  - Case report
OT  - Clinical genomics
OT  - Genetic analysis
OT  - Multiple endocrine neoplasia type 1
OT  - Somatic mutation
OT  - Whole-exome sequencing
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The Institutional Review Board of 
      Chungbuk National University Hospital and Korea National Institutes of Health 
      (NIH) approved this study. All of participants were informed to participate in 
      this study with written consents. CONSENT FOR PUBLICATION: Written informed 
      consent were obtained from the patient for the publication of their clinical 
      details and images. COMPETING INTERESTS: The authors declare that they have no 
      competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with 
      regard to jurisdictional claims in published maps and institutional affiliations.
EDAT- 2017/10/04 06:00
MHDA- 2017/10/14 06:00
PMCR- 2017/10/02
CRDT- 2017/10/04 06:00
PHST- 2016/12/28 00:00 [received]
PHST- 2017/09/11 00:00 [accepted]
PHST- 2017/10/04 06:00 [entrez]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2017/10/14 06:00 [medline]
PHST- 2017/10/02 00:00 [pmc-release]
AID - 10.1186/s12881-017-0465-9 [pii]
AID - 465 [pii]
AID - 10.1186/s12881-017-0465-9 [doi]
PST - epublish
SO  - BMC Med Genet. 2017 Oct 2;18(1):106. doi: 10.1186/s12881-017-0465-9.