ERBB2 Y772_A775DUP

在肺腺癌中，her2激酶域的突变发生率为2-4%，其中大部分发生在外显子20，如在一个小的8密码子区域（774-781或775-782）的帧复制或插入。这些类似于在eGFR-tk域中发现的外显子20的改变。m774插入，m774insayvm，占所有已鉴定的her2激酶域突变的62.5%（当与a775insyvma突变结合时，它们转化为相同的氨基酸序列变化）。如小鼠模型（Perrera等人，PNAS 2009）和随后的人类肺腺癌植入术临床试验所示，Her2-YVMA突变体预测了几种靶向Her2激动剂（如阿法替尼、曲妥珠单抗、奈拉汀尼和TDM-1（曲妥珠单抗-emtansine））作为单一疗法或联合特定化疗的反应。
Mutations in the HER2 kinase domain occur at a 2-4% frequency in lung adenocarcinomas, the majority of which are in exon 20 as in-frame duplications or insertions in a small 8 codon region (774-781 or 775-782). These are analogous to the exon 20 alterations found in EGFR TK domain. The M774 insertion, M774insAYVM, represents 62.5% of all HER2 kinase domain mutations identified (when combined with the A775insYVMA mutations as they translate to the identical amino acid sequence changes). As demonstrated in mouse models (Perrera et al., PNAS 2009) and subsequent clinical trials in human lung adenocarcinoma with these insertions, HER2 YVMA mutants predict response to several targeted HER2 agonists such as afatinib, trastuzumab, neratinib and TDM-1 (trastuzumab emtansine) as monotherapy or combined with specific chemotherapies.