PMID- 33840689
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1880-313X (Electronic)
IS  - 0388-6107 (Linking)
VI  - 42
IP  - 2
DP  - 2021
TI  - Genomic profiling of multiple tissues in two patients with multiple endocrine 
      neoplasia type 1.
PG  - 89-94
LID - 10.2220/biomedres.42.89 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor 
      syndrome. This hereditary cancer is caused by germline variants in MEN1. Two 
      patients with MEN1 were identified via whole exome sequencing and gene expression 
      profile analysis, conducted for 5,063 patients with various types of cancers. We 
      obtained multiple tumors from each patient; tumors derived from these two MEN1 
      patients had a loss of the normal MEN1 allele and frequently chromosomal copy 
      number changes. Thus, we investigated whether structural variants were present in 
      the MEN1 patient genomes. Whole-genome sequencing revealed no catastrophic 
      rearrangements, and the tumor samples had very low somatic variants. The two 
      patients had germline variants in MEN1 and some chromosomal copy number changes 
      including on chromosome 11. The only pathogenic variant detected was the MEN1 
      germline variant, and chromosomal rearrangements led to tumorigenesis in somatic 
      cells. Furthermore, the MEN1 tumor samples displayed a specific signature 
      characterized by T:A>C:G transition. Studies of multiple tumors obtained from 
      single patients are rare in hereditary cancer syndromes, and our results provide 
      insights that the second hit of the tumor suppressor gene MEN1 may be caused by a 
      gross genome rearrangement, not a small insertion and deletion, nor a change in 
      epigenetic regulation.
FAU - Naruoka, Akane
AU  - Naruoka A
AD  - Drug Discovery and Development Division, Shizuoka Cancer Center Research 
      Institute.
FAU - Ohnami, Sumiko
AU  - Ohnami S
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute.
FAU - Nagashima, Takeshi
AU  - Nagashima T
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute.
AD  - SRL Inc.
FAU - Serizawa, Masakuni
AU  - Serizawa M
AD  - Drug Discovery and Development Division, Shizuoka Cancer Center Research 
      Institute.
FAU - Hatakeyama, Keiichi
AU  - Hatakeyama K
AD  - Medical Genetics Division, Shizuoka Cancer Center Research Institute.
FAU - Ohshima, Keiichi
AU  - Ohshima K
AD  - Medical Genetics Division, Shizuoka Cancer Center Research Institute.
FAU - Ohnami, Shumpei
AU  - Ohnami S
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute.
FAU - Urakami, Kenichi
AU  - Urakami K
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute.
FAU - Horiuchi, Yasue
AU  - Horiuchi Y
AD  - Division of Genetic Counseling, Shizuoka Cancer Center Hospital.
FAU - Kiyozumi, Yoshimi
AU  - Kiyozumi Y
AD  - Division of Genetic Counseling, Shizuoka Cancer Center Hospital.
FAU - Matsubayashi, Hiroyuki
AU  - Matsubayashi H
AD  - Division of Genetic Counseling, Shizuoka Cancer Center Hospital.
FAU - Abe, Masato
AU  - Abe M
AD  - Division of Pathology, Shizuoka Cancer Center Hospital.
FAU - Ohishi, Takuma
AU  - Ohishi T
AD  - Division of Pathology, Shizuoka Cancer Center Hospital.
FAU - Kameya, Toru
AU  - Kameya T
AD  - Division of Pathology, Shizuoka Cancer Center Hospital.
FAU - Sugino, Takashi
AU  - Sugino T
AD  - Division of Pathology, Shizuoka Cancer Center Hospital.
FAU - Onitsuka, Tetsuro
AU  - Onitsuka T
AD  - Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital.
FAU - Isaka, Mitsuhiro
AU  - Isaka M
AD  - Division of Thoracic Surgery, Shizuoka Cancer Center Hospital.
FAU - Ohde, Yasuhisa
AU  - Ohde Y
AD  - Division of Thoracic Surgery, Shizuoka Cancer Center Hospital.
FAU - Sugiura, Teiichi
AU  - Sugiura T
AD  - Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital.
FAU - Ito, Takaaki
AU  - Ito T
AD  - Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital.
FAU - Uesaka, Katsuhiko
AU  - Uesaka K
AD  - Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital.
FAU - Akiyama, Yasuto
AU  - Akiyama Y
AD  - Immunotherapy Division, Shizuoka Cancer Center Research Institute.
FAU - Kusuhara, Masatoshi
AU  - Kusuhara M
AD  - Shizuoka Cancer Center.
FAU - Yamaguchi, Ken
AU  - Yamaguchi K
AD  - Shizuoka Cancer Center.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Japan
TA  - Biomed Res
JT  - Biomedical research (Tokyo, Japan)
JID - 8100317
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Chromosomes/*genetics
MH  - DNA Mutational Analysis
MH  - *Epigenesis, Genetic
MH  - Exons
MH  - Gastrinoma/genetics
MH  - *Gene Expression Profiling
MH  - *Gene Rearrangement
MH  - Genetic Variation
MH  - Genome, Human
MH  - *Genomics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Mutation
MH  - Neuroendocrine Tumors/*genetics
MH  - Proto-Oncogene Proteins/*genetics
EDAT- 2021/04/13 06:00
MHDA- 2021/12/21 06:00
CRDT- 2021/04/12 06:08
PHST- 2021/04/12 06:08 [entrez]
PHST- 2021/04/13 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
AID - 10.2220/biomedres.42.89 [doi]
PST - ppublish
SO  - Biomed Res. 2021;42(2):89-94. doi: 10.2220/biomedres.42.89.