Linked Life Data

18296683

Source:http://linkedlifedata.com/resource/pubmed/id/18296683

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-4-2
pubmed:abstractText
One of the most useful tools for investigating the aetiopathology of cancer is the mutation spectrum, which comprises the type and distribution of mutations within a gene sequence. Many studies have generated mutagen-induced spectra using in vitro or in vivo model systems in an attempt to find correlations with those observed in cancer-associated genes such as the TP53 tumour suppressor gene. Consequently, meaningful similarities in the types of mutation found in induced and human spectra have been demonstrated. However, it is more difficult to draw such conclusions about the distribution or sequence context of mutations when they arise in different target sequences. We have developed an analytical approach for base substitution spectra that capture information for both sequence context and mutation type simultaneously. The resulting mutation signature is a fixed set of data points that allows comparison of multiple mutation spectra regardless of sequence. We have applied this method to a mixed set of mutation spectra observed in exons 5, 7 and 8 of TP53 from cancers of brain, breast, skin, colon, oesophagus, liver, head and neck, stomach and lung (smokers and non-smokers) and spectra induced by benzo[a]pyrene diol epoxide, ultraviolet (UV) B, UVC, simulated sunlight and hydroxyl radicals in the cII, supF and yeast p53 model systems. We demonstrate that this approach allows human cancer and mutagen-induced signatures to be grouped together according to similarity. Specifically, the analysis reveals key differences between smoking- and non-smoking-related lung cancer for TP53 mutations and the mutability of CpG sites between exons in skin cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
772-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Comparison of induced and cancer-associated mutational spectra using multivariate data analysis.
pubmed:affiliation
Cancer Informatics Group, Institute of Life Science, Swansea Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, UK. p.d.lewis@swansea.ac.uk
pubmed:publicationType
Journal Article