PMID- 14648662
OWN - NLM
STAT- MEDLINE
DCOM- 20040227
LR  - 20171116
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 201
IP  - 4
DP  - 2003 Dec
TI  - Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma.
PG  - 589-95
AB  - Cyclin E overexpression occurs in a subset of endometrial carcinomas (ECs), but 
      the molecular mechanisms underlying this alteration remain to be established. The 
      present study has analysed amplification of the cyclin E gene (CCNE) and mutation 
      in hCDC4, the gene coding for the F-box protein, which tags phosphorylated cyclin 
      E for proteosomal degradation, to ascertain whether these alterations might be 
      responsible for cyclin E overexpression in ECs. Cyclin E and p53 expression was 
      studied by immunohistochemistry in eight atypical endometrial hyperplasias 
      (AEHs), 51 endometrioid endometrial carcinomas (EECs), and 22 non-endometrioid 
      endometrial carcinomas (NEECs). CCNE amplification was analysed by fluorescence 
      in situ hybridization (FISH). Mutations in exons 2-11 of the hCDC4 gene were 
      screened by PCR-SSCP-sequencing. Finally, the polymorphic marker D4S1610 was used 
      to assess loss of heterozygosity (LOH) in the hCDC4 gene. Cyclin E overexpression 
      was found in 26/81 (32%) cases and was associated with the histological type of 
      the lesion, since it was not found in any AEHs but was present in 27% of EECs and 
      54.5% of NEECs (p=0.035). Cyclin E overexpression was associated with 
      histological grade (p=0.011) and p53 immunostaining in EECs (p=0.033). CCNE 
      amplification was found in 6 of 37 (16%) ECs examined. There was a significant 
      association between CCNE amplification and the histological type of the lesion, 
      since five (83%) of the six cases with amplification were NEECs (p=0.008). One 
      EEC harboured an hCDC4 mutation: a CGA to CAA (Arg/Gln) change at codon 479. In 
      addition, D4S1610 LOH was found in 7 of 23 (30%) informative cases analysed, but 
      no correlation with cyclin E overexpression was found. However, the tumour with 
      hCDC4 mutation also showed LOH. This is the first study demonstrating that cyclin 
      E overexpression is associated with gene amplification in ECs, these alterations 
      being more frequent in NEECs. Although hCDC4 exhibits a low mutation frequency in 
      ECs overexpressing cyclin E, it seems to function as a tumour suppressor gene 
      that is involved in endometrial carcinogenesis.
CI  - Copyright 2003 John Wiley & Sons, Ltd.
FAU - Cassia, Raul
AU  - Cassia R
AD  - Laboratory of Breast and Gynaecological Cancer, Centro Nacional de 
      Investigaciones Oncologicas, Madrid, Spain.
FAU - Moreno-Bueno, Gema
AU  - Moreno-Bueno G
FAU - Rodriguez-Perales, Sandra
AU  - Rodriguez-Perales S
FAU - Hardisson, David
AU  - Hardisson D
FAU - Cigudosa, Juan C
AU  - Cigudosa JC
FAU - Palacios, Jose
AU  - Palacios J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin E)
RN  - 0 (F-Box Proteins)
RN  - 0 (F-Box-WD Repeat-Containing Protein 7)
RN  - 0 (FBXW7 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Base Sequence
MH  - Cell Cycle Proteins/*genetics
MH  - Cyclin E/*genetics/metabolism
MH  - Endometrial Neoplasms/*genetics
MH  - Exons/genetics
MH  - F-Box Proteins/*genetics
MH  - F-Box-WD Repeat-Containing Protein 7
MH  - Female
MH  - Gene Amplification/*genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Genes, Suppressor
MH  - Genes, p53/genetics
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Loss of Heterozygosity/genetics
MH  - Mutation/genetics
MH  - Phosphorylation
MH  - Ubiquitin-Protein Ligases/*genetics
EDAT- 2003/12/04 05:00
MHDA- 2004/02/28 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/02/28 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - 10.1002/path.1474 [doi]
PST - ppublish
SO  - J Pathol. 2003 Dec;201(4):589-95. doi: 10.1002/path.1474.