Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells

Hafid Alazzouzi; Gianpaolo Suriano; Angel Guerra; Alberto Plaja; Eloi Espín; Manel Armengol; Pia Alhopuro; Sergia Velho; Yasuhisa Shinomura; Juan José González-Aguilera; Hiroyuki Yamamoto; Lauri A. Aaltonen; Victor Moreno; Gabriel Capellà; Miguel Angel Peinado; Raquel Seruca; Diego Arango; Simó Schwartz

doi:10.1136/jmg.2006.042572

Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells

Hafid Alazzouzi, Gianpaolo Suriano, Angel Guerra, Alberto Plaja, Eloi Espín, Manel Armengol, Pia Alhopuro, Sergia Velho, Yasuhisa Shinomura, Juan José González-Aguilera, Hiroyuki Yamamoto, Lauri A. Aaltonen, Victor Moreno, Gabriel Capellà, Miguel Angel Peinado, Raquel Seruca, Diego Arango, Simó Schwartz^*

^*Corresponding author for this work

Department of Surgery

Research output: Contribution to journal › Article › Research › peer-review

25 Citations (Scopus)

Abstract

Background: Mdm2 is a natural inhibitor of p53 function and its overexpression impairs p53 transcriptional activity. T→G single-nucleotide polymorphism at position 309 (SNP309) of mdm2 induces overexpression of mdm2, but inhibits p53. Objectives: To determine whether SNP309 is a risk-modifier polymorphism in colorectal cancer (CRC) and whether tumour selection of P53 mutations are influenced by SNP309. Methods: Single-stranded conformation polymorphism and automatic sequencing were performed. Results: SNP309 is not associated with the risk of CRC or recurrence of tumours. These data do not over-ride the tumour-selection capabilities of P53 mutations in CRC. However, a significant association with non-dominant-negative P53 mutations (p = 0.02) was found. Conclusions: MDM2-SNP309 favours tumour selection of non-dominant negative P53 mutations in CRC, which also show an earlier age of tumour onset.

Original language	English
Pages (from-to)	75-80
Number of pages	6
Journal	Journal of Medical Genetics
Volume	44
Issue number	1
DOIs	https://doi.org/10.1136/jmg.2006.042572
Publication status	Published - Jan 2007

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Alazzouzi, H., Suriano, G., Guerra, A., Plaja, A., Espín, E., Armengol, M., Alhopuro, P., Velho, S., Shinomura, Y., González-Aguilera, J. J., Yamamoto, H., Aaltonen, L. A., Moreno, V., Capellà, G., Peinado, M. A., Seruca, R., Arango, D., & Schwartz, S. (2007). Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells. Journal of Medical Genetics, 44(1), 75-80. https://doi.org/10.1136/jmg.2006.042572

@article{f6027247f13e4c7cbb329c9a94f0b87d,

title = "Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells",

abstract = "Background: Mdm2 is a natural inhibitor of p53 function and its overexpression impairs p53 transcriptional activity. T→G single-nucleotide polymorphism at position 309 (SNP309) of mdm2 induces overexpression of mdm2, but inhibits p53. Objectives: To determine whether SNP309 is a risk-modifier polymorphism in colorectal cancer (CRC) and whether tumour selection of P53 mutations are influenced by SNP309. Methods: Single-stranded conformation polymorphism and automatic sequencing were performed. Results: SNP309 is not associated with the risk of CRC or recurrence of tumours. These data do not over-ride the tumour-selection capabilities of P53 mutations in CRC. However, a significant association with non-dominant-negative P53 mutations (p = 0.02) was found. Conclusions: MDM2-SNP309 favours tumour selection of non-dominant negative P53 mutations in CRC, which also show an earlier age of tumour onset.",

author = "Hafid Alazzouzi and Gianpaolo Suriano and Angel Guerra and Alberto Plaja and Eloi Esp{\'i}n and Manel Armengol and Pia Alhopuro and Sergia Velho and Yasuhisa Shinomura and Gonz{\'a}lez-Aguilera, \{Juan Jos{\'e}\} and Hiroyuki Yamamoto and Aaltonen, \{Lauri A.\} and Victor Moreno and Gabriel Capell{\`a} and Peinado, \{Miguel Angel\} and Raquel Seruca and Diego Arango and Sim{\'o} Schwartz",

year = "2007",

month = jan,

doi = "10.1136/jmg.2006.042572",

language = "English",

volume = "44",

pages = "75--80",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

publisher = "BMJ Publishing Group",

number = "1",

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Alazzouzi, H, Suriano, G, Guerra, A, Plaja, A, Espín, E , Armengol, M, Alhopuro, P, Velho, S, Shinomura, Y, González-Aguilera, JJ, Yamamoto, H, Aaltonen, LA, Moreno, V, Capellà, G, Peinado, MA, Seruca, R, Arango, D & Schwartz, S 2007, 'Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells', Journal of Medical Genetics, vol. 44, no. 1, pp. 75-80. https://doi.org/10.1136/jmg.2006.042572

TY - JOUR

T1 - Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells

AU - Alazzouzi, Hafid

AU - Suriano, Gianpaolo

AU - Guerra, Angel

AU - Plaja, Alberto

AU - Espín, Eloi

AU - Armengol, Manel

AU - Alhopuro, Pia

AU - Velho, Sergia

AU - Shinomura, Yasuhisa

AU - González-Aguilera, Juan José

AU - Yamamoto, Hiroyuki

AU - Aaltonen, Lauri A.

AU - Moreno, Victor

AU - Capellà, Gabriel

AU - Peinado, Miguel Angel

AU - Seruca, Raquel

AU - Arango, Diego

AU - Schwartz, Simó

PY - 2007/1

Y1 - 2007/1

N2 - Background: Mdm2 is a natural inhibitor of p53 function and its overexpression impairs p53 transcriptional activity. T→G single-nucleotide polymorphism at position 309 (SNP309) of mdm2 induces overexpression of mdm2, but inhibits p53. Objectives: To determine whether SNP309 is a risk-modifier polymorphism in colorectal cancer (CRC) and whether tumour selection of P53 mutations are influenced by SNP309. Methods: Single-stranded conformation polymorphism and automatic sequencing were performed. Results: SNP309 is not associated with the risk of CRC or recurrence of tumours. These data do not over-ride the tumour-selection capabilities of P53 mutations in CRC. However, a significant association with non-dominant-negative P53 mutations (p = 0.02) was found. Conclusions: MDM2-SNP309 favours tumour selection of non-dominant negative P53 mutations in CRC, which also show an earlier age of tumour onset.

AB - Background: Mdm2 is a natural inhibitor of p53 function and its overexpression impairs p53 transcriptional activity. T→G single-nucleotide polymorphism at position 309 (SNP309) of mdm2 induces overexpression of mdm2, but inhibits p53. Objectives: To determine whether SNP309 is a risk-modifier polymorphism in colorectal cancer (CRC) and whether tumour selection of P53 mutations are influenced by SNP309. Methods: Single-stranded conformation polymorphism and automatic sequencing were performed. Results: SNP309 is not associated with the risk of CRC or recurrence of tumours. These data do not over-ride the tumour-selection capabilities of P53 mutations in CRC. However, a significant association with non-dominant-negative P53 mutations (p = 0.02) was found. Conclusions: MDM2-SNP309 favours tumour selection of non-dominant negative P53 mutations in CRC, which also show an earlier age of tumour onset.

UR - https://www.scopus.com/pages/publications/33846443195

U2 - 10.1136/jmg.2006.042572

DO - 10.1136/jmg.2006.042572

M3 - Article

C2 - 16825434

AN - SCOPUS:33846443195

SN - 0022-2593

VL - 44

SP - 75

EP - 80

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 1

ER -

Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells

Abstract

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