PMID- 17519308
OWN - NLM
STAT- MEDLINE
DCOM- 20070917
LR  - 20220408
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 92
IP  - 8
DP  - 2007 Aug
TI  - Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia.
PG  - 3321-5
AB  - CONTEXT: Germline mutations in the MEN1 gene predispose to multiple endocrine 
      neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no 
      MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, 
      encoding p27(Kip1), was reported in one suspected MEN1 family with two 
      acromegalic patients. OBJECTIVE: Our objective was to evaluate the role of 
      CDKN1B/p27(Kip1) in human tumor predisposition in patients clinically suspected 
      of MEN1 but testing negative for MEN1 germline mutation as well as in familial 
      and sporadic acromegaly/pituitary adenoma patients. DESIGN: Genomic DNA was 
      analyzed for germline mutations in the CDKN1B/p27(Kip1) gene by PCR amplification 
      and direct sequencing. SETTING: The study was conducted at nonprofit academic 
      research and medical centers. PATIENTS: Thirty-six Dutch and one German suspected 
      MEN1 patient, who previously tested negative for germline MEN1 gene mutations, 
      were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary 
      adenoma patients from Europe and the United States were included in the study. 
      MAIN OUTCOME MEASURES: We analyzed germline CDKN1B/p27(Kip1) mutations in 
      individuals with pituitary adenoma and MEN1-like features. RESULTS: A 
      heterozygous 19-bp duplication (c.59_77dup19) leading to a truncated protein 
      product was identified in one Dutch patient with suspected MEN1 phenotype, 
      pituitary adenoma, carcinoid tumor, and hyperparathyroidism (one of 36, 2.8%). No 
      mutations were detected in either familial or sporadic acromegaly/pituitary 
      adenoma patients. CONCLUSIONS: Our results support the previous finding that 
      germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition. 
      However, such mutations appear uncommon in suspected MEN1 cases and rare or 
      nonexistent in familial or sporadic acromegaly/pituitary adenoma patients.
FAU - Georgitsi, Marianthi
AU  - Georgitsi M
AD  - Department of Medical Genetics, University of Helsinki, Finland.
FAU - Raitila, Anniina
AU  - Raitila A
FAU - Karhu, Auli
AU  - Karhu A
FAU - van der Luijt, Rob B
AU  - van der Luijt RB
FAU - Aalfs, Cora M
AU  - Aalfs CM
FAU - Sane, Timo
AU  - Sane T
FAU - Vierimaa, Outi
AU  - Vierimaa O
FAU - Makinen, Markus J
AU  - Makinen MJ
FAU - Tuppurainen, Karoliina
AU  - Tuppurainen K
FAU - Paschke, Ralph
AU  - Paschke R
FAU - Gimm, Oliver
AU  - Gimm O
FAU - Koch, Christian A
AU  - Koch CA
FAU - Gundogdu, Sadi
AU  - Gundogdu S
FAU - Lucassen, Anneke
AU  - Lucassen A
FAU - Tischkowitz, Marc
AU  - Tischkowitz M
FAU - Izatt, Louise
AU  - Izatt L
FAU - Aylwin, Simon
AU  - Aylwin S
FAU - Bano, Gul
AU  - Bano G
FAU - Hodgson, Shirley
AU  - Hodgson S
FAU - De Menis, Ernesto
AU  - De Menis E
FAU - Launonen, Virpi
AU  - Launonen V
FAU - Vahteristo, Pia
AU  - Vahteristo P
FAU - Aaltonen, Lauri A
AU  - Aaltonen LA
LA  - eng
SI  - GENBANK/EF474465
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070522
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (CDKN1B protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Computer Simulation
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - DNA/*genetics
MH  - DNA Mutational Analysis
MH  - Germ-Line Mutation
MH  - Humans
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Molecular Sequence Data
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2007/05/24 09:00
MHDA- 2007/09/18 09:00
CRDT- 2007/05/24 09:00
PHST- 2007/05/24 09:00 [pubmed]
PHST- 2007/09/18 09:00 [medline]
PHST- 2007/05/24 09:00 [entrez]
AID - jc.2006-2843 [pii]
AID - 10.1210/jc.2006-2843 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2007 Aug;92(8):3321-5. doi: 10.1210/jc.2006-2843. Epub 
      2007 May 22.