Department of Surgical Oncology, Institut Curie, Paris, France.
Anticancer Res. 2010 Oct;30(10):4229-35.
KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination.
KRAS 体细胞突变是转移性结直肠癌 (mCRC) 患者对 EGFR 靶向单克隆抗体无反应的主要预测因素。我们比较了 38 例 mCRC 患者的原发肿瘤和相应转移灶(1 至 4 个部位)中的 KRAS 突变状态。使用直接测序、SNAPShot 多重 PCR 和 Scorpion Taqman PCR 分析来分析 KRAS 突变状态。结果显示 54%的原发肿瘤存在 KRAS 突变。在原发灶和转移灶之间观察到 97%的一致性。在 5%的 mCRC 中也显示出肿瘤异质性。一例有三个不同的原发肿瘤,携带三种不同的 KRAS 突变,而在该患者的唯一转移灶中仅代表一种。我们得出结论,原发肿瘤和转移灶之间的 KRAS 状态具有高度一致性。更多的信息块和更敏感的检测方法可能会提高 KRAS 状态确定的准确性。