The presence of a TP53 gene mutation can influence tumour response to some treatments, especially in breast cancer. In this study, we analysed p53 mRNA expression, LOH at 17p13 and TP53 mutations from exons 2 to
11 in 206 patients with
breast carcinoma and correlated the results with disease-free and overall
survival. The observed mutations were classified according to their type and location
in the three protein domains (transactivation domain, DNA binding domain,
oligomerization domain) and correlated with disease-free and overall survival.
In our population, neither p53 mRNA expression nor LOH correlated with outcome.
Concerning TP53 mutations, 27% of tumours were mutated (53/197) and the
presence of a mutation in the TP53 gene was associated with worse overall
survival (p = 0.0026) but not with disease-free survival (p = 0.0697),
with median survival of 80 months and 78 months, respectively. When alterations
were segregated into mutation categories and locations, and related to
survival, tumours harbouring mutations other than missense mutations in the DNA
binding domain of P53 had the same survival profiles as wild-type tumours. Concerning
missense mutations in the DNA binding domain, median disease-free and overall
survival was 23 months and 35 months, respectively (p = 0.0021 and
p<0.0001, respectively), compared with 78 and 80 months in mutated tumours
overall. This work shows that disease-free and overall survival in patients
with a frameshift mutation of TP53 or missense mutation in the oligomerization
domain are the same as those in wild-type TP53 patients.
Source: Only missense mutations affecting the DNA binding domain of p53 influence outcomes in patients with breast carcinoma. Végran F, Rebucci M, Chevrier S, Cadouot M, Boidot R (email@example.com), Lizard-Nacol S. PLoS One. 2013;8(1):e55103.
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