PMID- 21289244
OWN - NLM
STAT- MEDLINE
DCOM- 20110614
LR  - 20220311
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 96
IP  - 4
DP  - 2011 Apr
TI  - Somatic mutation and germline sequence abnormalities in CDKN1B, encoding p27Kip1, 
      in sporadic parathyroid adenomas.
PG  - E701-6
LID - 10.1210/jc.2010-1338 [doi]
AB  - CONTEXT: Typical nonfamilial (sporadic) parathyroid adenomas are common endocrine 
      tumors for which no predisposing germline DNA variants and only a few clonally 
      altered genes that drive parathyroid tumorigenesis have been identified. CDKN1B, 
      encoding cyclin-dependent kinase inhibitor p27(kip1), has recently been 
      implicated in a multiple endocrine tumor phenotype in rats and, rarely, in a 
      human familial MEN1 (multiple endocrine neoplasia type 1)-like disorder. 
      OBJECTIVE: We sought to determine whether mutation of CDKN1B might contribute to 
      the development of common sporadic parathyroid adenomas. PATIENTS AND DESIGN: We 
      sequenced the CDKN1B gene in 86 parathyroid adenomas from patients with typical, 
      sporadic presentations of primary hyperparathyroidism. Identified alterations 
      were categorized as somatic or germline, and their functional consequences were 
      examined. RESULTS: CDKN1B sequence abnormalities were identified in four 
      parathyroid adenomas. Acquired biallelic alteration of CDKN1B, resulting from 
      somatic mutation plus loss of heterozygosity, was detected in one tumor. Germline 
      origin was documented in two cases despite nonfamilial presentations. None of the 
      observed alterations were found in 240 CDKN1B alleles from normal individuals, 
      nor among more than 2,000 previously reported alleles. Most identified variants 
      reduced p27(kip1) protein levels or altered in vitro stability. CONCLUSIONS: In 
      typical, sporadic parathyroid adenomas, CDKN1B mutation can be somatic and 
      clonal, indicative of a directly conferred selective advantage in parathyroid 
      tumorigenesis. Additionally, the identification of germline CDKN1B variants in 
      patients with sporadic presentations provides evidence for CDKN1B as a 
      susceptibility gene in the development of typical parathyroid adenomas.
FAU - Costa-Guda, Jessica
AU  - Costa-Guda J
AD  - Center for Molecular Medicine, University of Connecticut Health Center, 
      Farmington, Connecticut 06030-3101, USA.
FAU - Marinoni, Ilaria
AU  - Marinoni I
FAU - Molatore, Sara
AU  - Molatore S
FAU - Pellegata, Natalia S
AU  - Pellegata NS
FAU - Arnold, Andrew
AU  - Arnold A
LA  - eng
GR  - F32 DE021307/DE/NIDCR NIH HHS/United States
GR  - T32 DE007302/DE/NIDCR NIH HHS/United States
GR  - 1F32-DE021307/DE/NIDCR NIH HHS/United States
GR  - 5T32-DE07302/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110202
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (CDKN1B protein, human)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Adenoma/*genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Cyclin-Dependent Kinase Inhibitor p27/*genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - *Germ-Line Mutation/physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation/physiology
MH  - Open Reading Frames/genetics
MH  - Parathyroid Neoplasms/*genetics
PMC - PMC3070245
EDAT- 2011/02/04 06:00
MHDA- 2011/06/15 06:00
PMCR- 2012/04/01
CRDT- 2011/02/04 06:00
PHST- 2011/02/04 06:00 [entrez]
PHST- 2011/02/04 06:00 [pubmed]
PHST- 2011/06/15 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - jc.2010-1338 [pii]
AID - 10-1338 [pii]
AID - 10.1210/jc.2010-1338 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2011 Apr;96(4):E701-6. doi: 10.1210/jc.2010-1338. Epub 
      2011 Feb 2.