Expression signatures of TP53 mutations in serous ovarian cancers
Expression signatures of TP53 mutations in serous ovarian cancers
复制标题
DOI：
10.1186/1471-2407-10-237
复制
发表时间：
2010-05-26
期刊：
影响因子：
3.8
通讯作者：
Berchuck, Andrew
中科院分区：
文献类型：
--
作者：
Bernardini, Marcus Q.;Baba, Tsukasa;Berchuck, Andrew
背景：TP 53基因突变非常常见，并且发生在浆液性卵巢癌进展的早期。与突变状态相关的基因表达模式可以提供深入了解病因学和生物学的diseases.Methods：TP 53编码区测序89冷冻浆液性卵巢癌，40早期（I/II）和49晚期（III/IV）。使用Affytek U133 A表达数据来定义基因表达模式的突变，突变类型和癌症stages.Results：错义或链终止（无效）突变TP 53被发现在59/89（66%）卵巢癌。早期癌症的无效突变率显著高于晚期疾病（38%对8%，p < 0.03）。在晚期病例中，突变在短期存活者中比在长期存活者中更普遍（81% vs. 30%，p = 0.0004）。基因表达模式具有在训练数据内预测TP 53状态的强大能力。通过使用早期与晚期疾病进行样本外预测，来自早期癌症的特征可以准确地（86%）预测晚期癌症的突变状态。结论：这是首次尝试定义卵巢癌中TP 53突变的基因组特征。TP 53突变的基因表达特征的模式可以被辨别，包括几个已知的p53靶基因或已经在乳腺癌中TP 53突变的表达特征的背景下描述的基因。
Background: Mutations in the TP53 gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease.Methods: The TP53 coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage.Results: Missense or chain terminating (null) mutations in TP53 were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict TP53 status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers.Conclusions: This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.