Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we screened for the K-ras exon 2 point mutations in a group of 87 gynecological neoplasms (82 endometrial carcinomas, four carcinomas of the uterine cervix and one uterine carcinosarcoma) using the non-isotopic PCR-SSCP-direct sequencing techniques. Direct sequencing analysis revealed CAA-->CAC (Gln-->His) K-ras codon 61 point mutations in two (2.4%) of the 82 endometrial carcinomas mentioned above. These two cases were endometrial endometrioid carcinomas at an early clinical stage of disease (stage IB and IC due to FIGO). Those endometrial carcinomas that showed K-ras exon 2 point mutations revealed a strong positivity for heterogeneous nuclear retinoblastoma protein staining; none of these, however, have had the K-ras codon 12 point mutation. In addition, there were no K-ras gene point mutations in three endometrial carcinomas lacking the Rb protein immunohistochemically. None of the cervical carcinomas tested had K-ras gene point mutations, whereas one carcinosarcoma harbored K-ras codon 61 point mutation (CAA-->CAC). In conclusion, our data support the view that K-ras exon 2 point mutations are rare events in human endometrial cancer. Rb and K-ras gene abnormalities may occur independently of each other during endometrial carcinogenesis in humans.
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PMID:K-ras exon 2 point mutations in human endometrial cancer. 1117 36

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.
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PMID:Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma. 1464 62