Detection of T790M Gefitinib Resistance Mutation in EGFR using the BEAMing method

表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs），如吉非替尼或厄洛替尼，是原发性EGFR突变的非小细胞肺癌（NSCLC）患者的有效治疗方法。然而，大多数最初对这些药物治疗有反应的患者将对EGFR TKIs产生耐药性。据报道，继发性EGFR T790M突变与获得性耐药相关。我们使用beam（珠状、乳状、扩增、磁性）检测原发肿瘤中T790M突变，这是检测微小突变等位基因最敏感的技术。目前，我们使用改进版的BEAMing可以在1/10,000的水平上检测点突变。我们在270例原发性EGFR突变的非小细胞肺癌中检测到20例的T790M突变等位基因。少量T790M突变等位基因的检测可能有助于预测非小细胞肺癌对TKIs的耐药性。

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib or erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients with primary EGFR mutations. However, most patients who initially respond to treatment with these drugs will develop resistance to EGFR TKIs. A secondary EGFR T790M mutation is reported to correlate with acquired resistance. We examined the T790M mutation in primary tumors with BEAMing (beads, emulsion, amplification, magnetic), which is the most sensitive technique to detect minor mutated alleles. Currently, we can detect point mutation at the level of 1/10,000 using an improved version of the BEAMing. We detected T790M mutant alleles in NSCLCs in 20 out of 270 NSCLCs with primary EGFR mutations. The detection of small fraction of T790M mutant alleles may be useful for predicting resistance of NSCLCs to TKIs.