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Mutations and polymorphisms in TP53 gene-an overview on the role in colorectal cancer

Naccarati, A.; Polakova, V.; Pardini, B.; Vodickova, L.; Hemminki, Kari LU ; Kumar, R. and Vodicka, P. (2012) In Mutagenesis 27(2). p.211-218
Abstract
A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of... (More)
A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of alterations in the TP53 gene, both somatic mutations and inherited sequence variations, in predisposition to CRC and in the prognosis and response to therapy. The available data from association studies have mostly shown contradictory outcomes. The majority of the studies were based on limited sample sizes and focussed on a limited number of polymorphisms, with main being the rs1042522 (Arg72Pro). Thus far, there is no possible generalisation of the role of TP53 as also a predictor of therapeutic response and prognosis. The effects of TP53, and its abnormalities, on the response of tumours to cytotoxic drugs, radiation and chemoradiation are complex. However, from studies it is emerging that the inherited genetics of TP53 pathway components could be utilised to further define patient populations in their abilities to induce p53 activity in response to either DNA damaging or p53-targeted therapies. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mutagenesis
volume
27
issue
2
pages
211 - 218
publisher
Oxford University Press
external identifiers
  • wos:000300040200010
  • scopus:84863414654
ISSN
0267-8357
DOI
10.1093/mutage/ger067
language
English
LU publication?
yes
id
20b4a6f4-82fd-47f5-9593-25b0345a116c (old id 2409782)
date added to LUP
2012-04-02 09:32:15
date last changed
2017-11-19 03:43:58
@article{20b4a6f4-82fd-47f5-9593-25b0345a116c,
  abstract     = {A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of alterations in the TP53 gene, both somatic mutations and inherited sequence variations, in predisposition to CRC and in the prognosis and response to therapy. The available data from association studies have mostly shown contradictory outcomes. The majority of the studies were based on limited sample sizes and focussed on a limited number of polymorphisms, with main being the rs1042522 (Arg72Pro). Thus far, there is no possible generalisation of the role of TP53 as also a predictor of therapeutic response and prognosis. The effects of TP53, and its abnormalities, on the response of tumours to cytotoxic drugs, radiation and chemoradiation are complex. However, from studies it is emerging that the inherited genetics of TP53 pathway components could be utilised to further define patient populations in their abilities to induce p53 activity in response to either DNA damaging or p53-targeted therapies.},
  author       = {Naccarati, A. and Polakova, V. and Pardini, B. and Vodickova, L. and Hemminki, Kari and Kumar, R. and Vodicka, P.},
  issn         = {0267-8357},
  language     = {eng},
  number       = {2},
  pages        = {211--218},
  publisher    = {Oxford University Press},
  series       = {Mutagenesis},
  title        = {Mutations and polymorphisms in TP53 gene-an overview on the role in colorectal cancer},
  url          = {http://dx.doi.org/10.1093/mutage/ger067},
  volume       = {27},
  year         = {2012},
}