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 -
