| Title: |
MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases |
| Authors: |
Nagy, E.; Gajjar, Ketan; Patel, Imran I.; Taylor, S.; Martin-Hirsch, Pierre Leonard; Stringfellow, Helen F.; Martin, Francis L; Phillips, David H. |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2014 |
| Collection: |
University of Central Lancashire: CLOK - Central Lancashire Online Knowledge |
| Subject Terms: |
B290 - Pharmacology; toxicology & pharmacy not elsewhere classified |
| Description: |
background: Tamoxifen has anti-oestrogenic and anti-tumour activity in the breast, but is oestrogenic and carcinogenic in the endometrium. It can induce experimental tumours by both hormonal and DNA-damaging mechanisms, but its carcinogenic mode of action in human endometrium remains unclear. methods: We investigated whether an epigenetic mechanism, involving promoter hypermethylation of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to the drug (EC, n=38). results: There were significant (PA, occurred in small numbers in both groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours and were of the type that has large impact on protein function, such as indel or nonsense mutations. These observations alongside the mutational spectrum in PTEN suggest that the malignancies arise from different backgrounds, hence pointing to an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation. This coincided with mutations more frequently in the TAM (78%) than in the EC (50%) group, even though there were significantly (P |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0007-0920 |
| Relation: |
https://clok.uclan.ac.uk/id/eprint/16261/1/16261_martin.pdf; Nagy, E., Gajjar, Ketan, Patel, Imran I., Taylor, S., Martin-Hirsch, Pierre Leonard, Stringfellow, Helen F., Martin, Francis L orcid iconorcid:0000-0001-8562-4944 and Phillips, David H. (2014) MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases. British Journal of Cancer, 110 (12). pp. 2874-2880. ISSN 0007-0920 |
| DOI: |
10.1038/bjc.2014.263 |
| Availability: |
https://clok.uclan.ac.uk/id/eprint/16261/; https://clok.uclan.ac.uk/id/eprint/16261/1/16261_martin.pdf; https://doi.org/10.1038/bjc.2014.263 |
| Rights: |
cc_by_nc_sa_4 |
| Accession Number: |
edsbas.50A815DC |
| Database: |
BASE |