Association of p53 Arg72Pro polymorphism and β-catenin accumulation in mycosis fungoides

B. Bellei, C. Cota, A. Amantea, L. Muscardin, M. Picardo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Aberrant activation of β-catenin contributes to the onset of a variety of tumours. There are many tumours that display β-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type β-catenin has been associated with mutational inactivation of the p53 tumour suppressor. Objectives: To investigate the potential role of p53 and its homologue p63 in β-catenin deregulation and to correlate this with disease outcome. Methods: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for β-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for β-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of β-catenin exon 3 and p53 exons 4-8. Results: Our findings revealed overexpression of β-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P <0.05) in the β-catenin- positive group (73%). Sequence analysis demonstrated that wild-type β-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with β-catenin overexpression (P <0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). Conclusions: We found an association of β-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for β-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving β-catenin and p53.

Original languageEnglish
Pages (from-to)1223-1229
Number of pages7
JournalBritish Journal of Dermatology
Volume155
Issue number6
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Catenins
Mycosis Fungoides
Cutaneous T-Cell Lymphoma
Mutation
Exons
Neoplasms
Microdissection
p53 Genes
Codon
Lasers
Immunohistochemistry

Keywords

  • β-catenin
  • Apoptosis
  • Cutaneous T-cell lymphoma
  • Mycosis fungoides
  • p53
  • Polymorphism

ASJC Scopus subject areas

  • Dermatology

Cite this

Association of p53 Arg72Pro polymorphism and β-catenin accumulation in mycosis fungoides. / Bellei, B.; Cota, C.; Amantea, A.; Muscardin, L.; Picardo, M.

In: British Journal of Dermatology, Vol. 155, No. 6, 12.2006, p. 1223-1229.

Research output: Contribution to journalArticle

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abstract = "Background: Aberrant activation of β-catenin contributes to the onset of a variety of tumours. There are many tumours that display β-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type β-catenin has been associated with mutational inactivation of the p53 tumour suppressor. Objectives: To investigate the potential role of p53 and its homologue p63 in β-catenin deregulation and to correlate this with disease outcome. Methods: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for β-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for β-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of β-catenin exon 3 and p53 exons 4-8. Results: Our findings revealed overexpression of β-catenin, p53 and p63 in 46{\%}, 38{\%} and 17{\%} of cases, respectively. The number of p53-positive cases of MF was significantly higher (P <0.05) in the β-catenin- positive group (73{\%}). Sequence analysis demonstrated that wild-type β-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with β-catenin overexpression (P <0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). Conclusions: We found an association of β-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for β-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving β-catenin and p53.",
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T1 - Association of p53 Arg72Pro polymorphism and β-catenin accumulation in mycosis fungoides

AU - Bellei, B.

AU - Cota, C.

AU - Amantea, A.

AU - Muscardin, L.

AU - Picardo, M.

PY - 2006/12

Y1 - 2006/12

N2 - Background: Aberrant activation of β-catenin contributes to the onset of a variety of tumours. There are many tumours that display β-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type β-catenin has been associated with mutational inactivation of the p53 tumour suppressor. Objectives: To investigate the potential role of p53 and its homologue p63 in β-catenin deregulation and to correlate this with disease outcome. Methods: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for β-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for β-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of β-catenin exon 3 and p53 exons 4-8. Results: Our findings revealed overexpression of β-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P <0.05) in the β-catenin- positive group (73%). Sequence analysis demonstrated that wild-type β-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with β-catenin overexpression (P <0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). Conclusions: We found an association of β-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for β-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving β-catenin and p53.

AB - Background: Aberrant activation of β-catenin contributes to the onset of a variety of tumours. There are many tumours that display β-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type β-catenin has been associated with mutational inactivation of the p53 tumour suppressor. Objectives: To investigate the potential role of p53 and its homologue p63 in β-catenin deregulation and to correlate this with disease outcome. Methods: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for β-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for β-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of β-catenin exon 3 and p53 exons 4-8. Results: Our findings revealed overexpression of β-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P <0.05) in the β-catenin- positive group (73%). Sequence analysis demonstrated that wild-type β-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with β-catenin overexpression (P <0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). Conclusions: We found an association of β-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for β-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving β-catenin and p53.

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KW - Polymorphism

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