| In vitro stability of APC gene sequences and the influence of DNA repair status. | |
| | |
MedLine Citation:
|
PMID: 22294772 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
APC is a key 'gatekeeper' gene in colorectal tumorigenesis. The high frequency of APC defects observed in colorectal cancer tissue is the result of selective growth advantage of cells with loss-of-function mutations at that locus. However, mutations may also arise due to inherent sequence instability. Defective DNA mismatch repair (MMR) and base excision repair (BER) also contribute to colorectal carcinogenesis and may compound such instability. To avoid the effect of clonal selective advantage imparted by APC mutation in cancer cells, we assessed in vitro APC mutation frequency in cell lines of lymphoid lineage to investigate the influence of defective MMR and BER. In DNA repair proficient cells, we observed substantially greater inherent sequence instability in APC gene coding sequences compared to reference sequences. Surprisingly, however, this difference was abrogated in MMR defective lines. We also found greater mutation frequency at exonic DNA sequences outwith the APC region in cells defective for either MMR or BER defects. The underlying propensity for mutation at the APC gene is intriguing, while the greater frequency of mutation in cells defective for DNA repair has relevance to understanding events leading to colorectal cancer and other malignancies. |
| | |
Authors:
|
Charlotte L Turnbull; Andrea L Bacon; Malcolm G Dunlop; Susan M Farrington |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Mutagenesis Volume: 27 ISSN: 1464-3804 ISO Abbreviation: Mutagenesis Publication Date: 2012 Mar |
Date Detail:
|
Created Date: 2012-02-01 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8707812 Medline TA: Mutagenesis Country: England |
Other Details:
|
Languages: eng Pagination: 233-8 Citation Subset: IM |
Affiliation:
|
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Differences in nucleotide excision repair capacity between newly diagnosed colorectal cancer patient...
Next Document: A review of the genetic background and tumour profiling in familial colorectal cancer.