PMID- 25456907
OWN - NLM
STAT- MEDLINE
DCOM- 20150218
LR  - 20181113
IS  - 1532-7361 (Electronic)
IS  - 0039-6060 (Print)
IS  - 0039-6060 (Linking)
VI  - 156
IP  - 6
DP  - 2014 Dec
TI  - Preliminary whole-exome sequencing reveals mutations that imply common 
      tumorigenicity pathways in multiple endocrine neoplasia type 1 patients.
PG  - 1351-7; discussion 1357-8
LID - S0039-6060(14)00551-0 [pii]
LID - 10.1016/j.surg.2014.08.073 [doi]
AB  - BACKGROUND: Whole-exome sequencing studies have not established definitive 
      somatic mutation patterns among patients with sporadic hyperparathyroidism (HPT). 
      No sequencing has evaluated multiple endocrine neoplasia type 1 (MEN1)-related 
      HPT. We sought to perform whole-exome sequencing in HPT patients to identify 
      somatic mutations and associated biological pathways and tumorigenic networks. 
      METHODS: Whole-exome sequencing was performed on blood and tissue from HPT 
      patients (MEN1 and sporadic) and somatic single nucleotide variants (SNVs) were 
      identified. Stop-gain and stop-loss SNVs were analyzed with Ingenuity Pathways 
      Analysis (IPA). Loss of heterozygosity (LOH) was also assessed. RESULTS: 
      Sequencing was performed on 4 MEN1 and 10 sporadic cases. Eighteen 
      stop-gain/stop-loss SNV mutations were identified in 3 MEN1 patients. One complex 
      network was identified on IPA: Cellular function and maintenance, tumor 
      morphology, and cardiovascular disease (IPA score = 49). A nonsynonymous SNV of 
      TP53 (lysine-to-glutamic acid change at codon 81) identified in a MEN1 patient 
      was suggested to be a driver mutation (Cancer-specific High-throughput Annotation 
      of Somatic Mutations; P = .002). All MEN1 and 3/10 sporadic specimens 
      demonstrated LOH of chromosome 11. CONCLUSION: Whole-exome sequencing revealed 
      somatic mutations in MEN1 associated with a single tumorigenic network, whereas 
      sporadic pathogenesis seemed to be more diverse. A somatic TP53 mutation was also 
      identified. LOH of chromosome 11 was seen in all MEN1 and 3 of 10 sporadic 
      patients.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Romero Arenas, Minerva Angelica
AU  - Romero Arenas MA
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX.
FAU - Fowler, Richard G
AU  - Fowler RG
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
FAU - San Lucas, F Anthony
AU  - San Lucas FA
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
FAU - Shen, Jie
AU  - Shen J
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
FAU - Rich, Thereasa A
AU  - Rich TA
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX.
FAU - Grubbs, Elizabeth G
AU  - Grubbs EG
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX.
FAU - Lee, Jeffrey E
AU  - Lee JE
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX.
FAU - Scheet, Paul
AU  - Scheet P
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
FAU - Perrier, Nancy D
AU  - Perrier ND
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX.
FAU - Zhao, Hua
AU  - Zhao H
AD  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX. Electronic address: HZhao2@mdanderson.org.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141111
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
SB  - IM
MH  - Adenoma/genetics/pathology
MH  - Adolescent
MH  - Adult
MH  - Carcinogenesis/*genetics
MH  - DNA Mutational Analysis
MH  - Exome/*genetics
MH  - Female
MH  - Genes, p53/*genetics
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Parathyroid Neoplasms/genetics/pathology
MH  - Pilot Projects
MH  - Sampling Studies
MH  - Sensitivity and Specificity
MH  - Young Adult
PMC - PMC4822541
MID - NIHMS772865
EDAT- 2014/12/03 06:00
MHDA- 2015/02/19 06:00
PMCR- 2016/04/06
CRDT- 2014/12/03 06:00
PHST- 2014/03/01 00:00 [received]
PHST- 2014/08/21 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/02/19 06:00 [medline]
PHST- 2016/04/06 00:00 [pmc-release]
AID - S0039-6060(14)00551-0 [pii]
AID - 10.1016/j.surg.2014.08.073 [doi]
PST - ppublish
SO  - Surgery. 2014 Dec;156(6):1351-7; discussion 1357-8. doi: 
      10.1016/j.surg.2014.08.073. Epub 2014 Nov 11.