International Agency for Research on Cancer, Group of Molecular Carcinogenesis, Lyon, France.
Curr Opin Oncol. 2011 Jan;23(1):88-92. doi: 10.1097/CCO.0b013e3283412dfa.
We used two examples of genes, TP53 and EGFR, which are somatically altered by intragenic mutations in common cancer types to illustrate how somatic mutations have followed very different routes to clinical applications.
TP53 somatic mutations are frequent in many cancers. Their prognostic and predictive values are currently assessed in several clinical trials and TP53 gene therapy is in use in China. Mutations in EGFR have been proved to be predictive of response to tyrosine kinase inhibitors, allowing for the licensing of gefitinib in lung adenocarcinomas carrying a mutated EGFR gene.
With the accumulation of knowledge on the predictive and prognostic value of somatic mutations, and with recent advances in large-scale sequencing techniques and reduction in cost of sequencing, sequencing several genes in human tumors is on the verge of becoming routine clinical practice.
我们使用了两个基因的例子,TP53 和 EGFR,它们在常见癌症类型中通过基因内突变而发生体细胞改变,以说明体细胞突变是如何遵循非常不同的途径来实现临床应用的。
TP53 体细胞突变在许多癌症中很常见。它们的预后和预测价值目前正在几项临床试验中进行评估,TP53 基因治疗在中国已经在使用中。EGFR 突变已被证明与对酪氨酸激酶抑制剂的反应有关,这使得携带 EGFR 基因突变的肺腺癌患者可以使用吉非替尼。
随着对体细胞突变的预测和预后价值的知识积累,以及大规模测序技术的最新进展和测序成本的降低,在人类肿瘤中对几个基因进行测序即将成为常规的临床实践。