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Effect of the codon 72 polymorphism (c.215G>C, p.Arg72Pro) in combination with somatic sequence variants in the TP53 gene on survival in patients with advanced ovarian carcinoma

✍ Scribed by Yun Wang; Pedro Kringen; Gunnar B. Kristensen; Ruth Holm; Mark M.O. Baekelandt; Magali Olivier; Hanne Skomedal; Pierre Hainaut; Claes G. Tropé; Vera M. Abeler; Jahn M. Nesland; Anne-Lise Børresen-Dale; Åslaug Helland


Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
522 KB
Volume
24
Category
Article
ISSN
1059-7794

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✦ Synopsis


This study was conducted to evaluate the frequency and prognostic impact of TP53 alterations stratified for the TP53 codon 72 polymorphism (c.215G4C, p.Arg72Pro) in a cohort of 109 patients with advanced ovarian carcinomas. TP53 sequence variants were observed in 80 of the 109 (73.4%) tumors and were significantly associated with grade of differentiation (P=0.001). A tendency towards higher frequency of sequence variants in tumors with higher FIGO stages was seen (P=0.05). The type of TP53 sequence variant (transition A:T4G:C vs. G:C4A:T at CpG dinucleotides, and transversion G:C4T:A) had significant correlation with patients' age (P=0.04) with more A:T4G:C in patients over 60 years old. No significant associations were found between frequency of sequence variants and age at diagnosis, histological type, size of residual tumor after primary surgery, or long-term survival. Analyses of the codon 72 polymorphism in tumor DNA gave a higher frequency of homozygosity/hemizygosity than expected from the population frequency, particularly for the Pro allele. Tumors homozygous or hemizygous for the Pro allele had significantly higher frequency of TP53 sequence variants, particularly of the nonmissense type (P=0.002), and patients with these types of alterations had significantly shorter survival (P=0.04). TP53 protein accumulation, determined by immunohistochemistry (IHC), was found in 67.9% (74 out of 109) of the tumors, was significantly more common among serous than nonserous ovarian carcinomas (P=0.008), and had a significant effect on progression-free survival (P=0.03). p63 (TP73L; formerly TP63) and p73 (TP73) protein accumulation detected by IHC was seen in 67.9 and 0% of the tumors, respectively. A significantly higher frequency of p63-positive cases was seen among serous tumors (P=0.008) and tended to increase with increasing FIGO stages (P=0.05), but had no significant effect on survival. No association between p63 protein accumulation and TP53 protein accumulation was seen.


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Effect of the codon 72 polymorphism (c.2
✍ Yun Wang; Pedro Kringen; Gunnar B. Kristensen; Ruth Holm; Mark M.O. Baekelandt; 📂 Article 📅 2006 🏛 John Wiley and Sons 🌐 English ⚖ 104 KB

The original article to which this Erratum refers was published in Human Mutation 24: 21-34 (2004). Using a newly developed method-Arrayed Primer Extension (APEX) and direct sequencing of exon 10 and 11 to reanalyze for TP53 sequence alterations-13 new mutations were identified. In addition, a few