PMID- 27742789
OWN - NLM
STAT- MEDLINE
DCOM- 20180131
LR  - 20220318
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 22
IP  - 20
DP  - 2016 Oct 15
TI  - Novel Genetic Causes of Pituitary Adenomas.
PG  - 5030-5042
AB  - Recently, a number of novel genetic alterations have been identified that 
      predispose individuals to pituitary adenomas. Clinically relevant pituitary 
      adenomas are relatively common, present in 0.1% of the general population. They 
      are mostly benign monoclonal neoplasms that arise from any of the five 
      hormone-secreting cell types of the anterior lobe of the pituitary gland, and 
      cause disease due to hormonal alterations and local space-occupying effects. The 
      pathomechanism of pituitary adenomas includes alterations in cell-cycle 
      regulation and growth factor signaling, which are mostly due to epigenetic 
      changes; somatic and especially germline mutations occur more rarely. A 
      significant proportion of growth hormone- and adrenocorticotrophin-secreting 
      adenomas have activating somatic mutations in the GNAS and USP8 genes, 
      respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, 
      often in a familial setting. Classical tumor predisposition syndromes include 
      multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney 
      complex, and McCune-Albright syndrome. Pituitary tumors have also been described 
      in association with neurofibromatosis type 1, DICER1 syndrome, and SDHx 
      mutations. Pituitary adenomas with no other associated tumors have been described 
      as familial isolated pituitary adenomas. Patients with AIP or GPR101 mutations 
      often present with pituitary gigantism either in a familial or simplex setting. 
      GNAS and GPR101 mutations that arise in early embryonic age can lead to somatic 
      mosaicism involving the pituitary gland and resulting in growth hormone excess. 
      Senescence has been suggested as the key mechanism protecting pituitary adenomas 
      turning malignant in the overwhelming majority of cases. Here we briefly 
      summarize the genetic background of pituitary adenomas, with an emphasis on the 
      recent developments in this field. Clin Cancer Res; 22(20); 5030-42. (c)2016 AACR 
      SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS REVISING 
      PARADIGMS".
CI  - (c)2016 American Association for Cancer Research.
FAU - Caimari, Francisca
AU  - Caimari F
AD  - Centre for Endocrinology, William Harvey Research Institute, Barts and the London 
      School of Medicine and Dentistry, Queen Mary University of London, London, United 
      Kingdom.
FAU - Korbonits, Marta
AU  - Korbonits M
AD  - Centre for Endocrinology, William Harvey Research Institute, Barts and the London 
      School of Medicine and Dentistry, Queen Mary University of London, London, United 
      Kingdom. m.korbonits@qmul.ac.uk.
LA  - eng
PT  - Editorial
PT  - Review
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Chromogranins)
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.19.12 (USP8 protein, human)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.6.1.- (GNAS protein, human)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
SB  - IM
MH  - Adenoma/*genetics/*pathology
MH  - Chromogranins/genetics
MH  - Endopeptidases/genetics
MH  - Endosomal Sorting Complexes Required for Transport/genetics
MH  - GTP-Binding Protein alpha Subunits, Gs/genetics
MH  - Germ-Line Mutation/genetics
MH  - Humans
MH  - Pituitary Gland, Anterior/*pathology
MH  - Pituitary Neoplasms/*genetics/*pathology
MH  - Proto-Oncogene Proteins/genetics
MH  - Ubiquitin Thiolesterase/genetics
EDAT- 2016/10/16 06:00
MHDA- 2018/02/01 06:00
CRDT- 2016/10/16 06:00
PHST- 2016/05/18 00:00 [received]
PHST- 2016/08/24 00:00 [accepted]
PHST- 2016/10/16 06:00 [entrez]
PHST- 2016/10/16 06:00 [pubmed]
PHST- 2018/02/01 06:00 [medline]
AID - 22/20/5030 [pii]
AID - 10.1158/1078-0432.CCR-16-0452 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2016 Oct 15;22(20):5030-5042. doi: 
      10.1158/1078-0432.CCR-16-0452.