PMID- 20154675
OWN - NLM
STAT- MEDLINE
DCOM- 20100415
LR  - 20230411
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 42
IP  - 3
DP  - 2010 Mar
TI  - Germline mutations in TMEM127 confer susceptibility to pheochromocytoma.
PG  - 229-33
LID - 10.1038/ng.533 [doi]
AB  - Pheochromocytomas, which are catecholamine-secreting tumors of neural crest 
      origin, are frequently hereditary. However, the molecular basis of the majority 
      of these tumors is unknown. We identified the transmembrane-encoding gene TMEM127 
      on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of 
      103 samples, we detected truncating germline TMEM127 mutations in approximately 
      30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas 
      without a known genetic cause. The wild-type allele was consistently deleted in 
      tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation. 
      Pheochromocytomas with mutations in TMEM127 are transcriptionally related to 
      tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of 
      mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro 
      gain-of-function and loss-of-function analyses indicate that TMEM127 is a 
      negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane 
      system and colocalizes with perinuclear (activated) mTOR, suggesting a 
      subcompartmental-specific effect. Our studies identify TMEM127 as a tumor 
      suppressor gene and validate the power of hereditary tumors to elucidate cancer 
      pathogenesis.
FAU - Qin, Yuejuan
AU  - Qin Y
AD  - Departments of Medicine, San Antonio, Texas, USA.
FAU - Yao, Li
AU  - Yao L
FAU - King, Elizabeth E
AU  - King EE
FAU - Buddavarapu, Kalyan
AU  - Buddavarapu K
FAU - Lenci, Romina E
AU  - Lenci RE
FAU - Chocron, E Sandra
AU  - Chocron ES
FAU - Lechleiter, James D
AU  - Lechleiter JD
FAU - Sass, Meghan
AU  - Sass M
FAU - Aronin, Neil
AU  - Aronin N
FAU - Schiavi, Francesca
AU  - Schiavi F
FAU - Boaretto, Francesca
AU  - Boaretto F
FAU - Opocher, Giuseppe
AU  - Opocher G
FAU - Toledo, Rodrigo A
AU  - Toledo RA
FAU - Toledo, Sergio P A
AU  - Toledo SP
FAU - Stiles, Charles
AU  - Stiles C
FAU - Aguiar, Ricardo C T
AU  - Aguiar RC
FAU - Dahia, Patricia L M
AU  - Dahia PL
LA  - eng
SI  - GEO/GSE19987
GR  - P30 CA54174/CA/NCI NIH HHS/United States
GR  - P30 CA054174-17/CA/NCI NIH HHS/United States
GR  - P01 AG019316/AG/NIA NIH HHS/United States
GR  - UL1 RR025767-02/RR/NCRR NIH HHS/United States
GR  - UL1 TR000149/TR/NCATS NIH HHS/United States
GR  - P30 CA054174/CA/NCI NIH HHS/United States
GR  - NIH-P30 CA54174/CA/NCI NIH HHS/United States
GR  - P01AG19316/AG/NIA NIH HHS/United States
GR  - UL1 RR025767/RR/NCRR NIH HHS/United States
GR  - P30 AG013319/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100214
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Membrane Proteins)
RN  - 0 (TMEM127 protein, human)
SB  - IM
MH  - Adrenal Gland Neoplasms/*genetics
MH  - Adult
MH  - Aged
MH  - Cells, Cultured
MH  - Cohort Studies
MH  - DNA Mutational Analysis
MH  - Family
MH  - Genetic Predisposition to Disease
MH  - *Germ-Line Mutation/physiology
MH  - Humans
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - Pheochromocytoma/*genetics
MH  - Polymorphism, Single Nucleotide/physiology
PMC - PMC2998199
MID - NIHMS172048
EDAT- 2010/02/16 06:00
MHDA- 2010/04/16 06:00
PMCR- 2010/12/07
CRDT- 2010/02/16 06:00
PHST- 2009/10/01 00:00 [received]
PHST- 2010/01/20 00:00 [accepted]
PHST- 2010/02/16 06:00 [entrez]
PHST- 2010/02/16 06:00 [pubmed]
PHST- 2010/04/16 06:00 [medline]
PHST- 2010/12/07 00:00 [pmc-release]
AID - ng.533 [pii]
AID - 10.1038/ng.533 [doi]
PST - ppublish
SO  - Nat Genet. 2010 Mar;42(3):229-33. doi: 10.1038/ng.533. Epub 2010 Feb 14.