纯合型MDM2-SNP309结直肠癌细胞中非显性负性P53突变的肿瘤选择优势
Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells.
作者信息
Alazzouzi Hafid, Suriano Gianpaolo, Guerra Angel, Plaja Alberto, Espín Eloi, Armengol Manel, Alhopuro Pia, Velho Sergia, Shinomura Yasuhisa, González-Aguilera Juan José, Yamamoto Hiroyuki, Aaltonen Lauri A, Moreno Víctor, Capellà Gabriel, Peinado Miguel Angel, Seruca Raquel, Arango Diego, Schwartz Simó
出版信息
J Med Genet. 2007 Jan;44(1):75-80. doi: 10.1136/jmg.2006.042572. Epub 2006 Jul 6.
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.
背景
Mdm2是p53功能的天然抑制剂，其过表达会损害p53的转录活性。mdm2第309位的T→G单核苷酸多态性（SNP309）会诱导mdm2过表达，但会抑制p53。
目的
确定SNP309是否为结直肠癌（CRC）的风险修饰多态性，以及P53突变的肿瘤选择是否受SNP309影响。
方法
进行单链构象多态性分析和自动测序。
结果
SNP309与CRC风险或肿瘤复发无关。这些数据并未推翻CRC中P53突变的肿瘤选择能力。然而，发现其与非显性负性P53突变存在显著关联（p = 0.02）。
结论
MDM2-SNP309有利于CRC中非显性负性P53突变的肿瘤选择，这些突变也显示出肿瘤发病年龄较早。
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