Somatic mutations of the HER2 in metastatic breast cancer
Somatic mutations of the HER2 in metastatic breast cancer
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转移性乳腺癌中 HER2 的体细胞突变
DOI：
10.1007/s13277-014-2414-y
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发表时间：
2014-12-01
期刊：
影响因子：
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通讯作者：
Wang, Jing
中科院分区：
文献类型：
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作者：
Fang, Yi;Jiang, Yanxia;Wang, Jing
肺癌中表皮生长因子受体基因（EGFR）突变可预测EGFR激酶抑制剂的敏感性。HER 2（也称为NEU、EGFR 2或ERBB 2）是EGFR受体酪氨酸激酶家族的成员，在某些人类癌症的发病机制中起重要作用，最近在肺癌中报告了突变。我们对198例转移性乳腺癌（MBC）以及34例其他上皮癌（膀胱癌、前列腺癌和结直肠癌）的HER 2全长进行了测序，并将突变状态与临床病理特征以及EGFR或KRAS突变的存在进行了比较。11.6%（23/198）的MBC存在HER 2突变，其他类型的癌症不存在。HER 2突变位于第15外显子，第20外显子的框内插入与EGFR插入的相应区域相同。曲妥珠单抗给药后，患者的HER 2突变频率显著更高（34.8%，8/23;P= 0.02）。外显子15和20的突变比野生型HER 2在激活信号转导和诱导存活、侵袭性和致瘤性方面更有效。
Mutations in the epidermal growth factor receptor gene (EGFR) in lung cancers predict for sensitivity to EGFR kinase inhibitors. HER2 (also known as NEU, EGFR2, or ERBB2) is a member of the EGFR family of receptor tyrosine kinases and plays important roles in the pathogenesis of certain human cancers, and mutations have recently been reported in lung cancers. We sequenced the full length of HER2 in 198 metastatic breast cancers (MBC) as well as 34 other epithelial cancers (bladder, prostate, and colorectal cancers) and compared the mutational status with clinic pathologic features and the presence of EGFR or KRAS mutations. HER2 mutations were present in 11.6 % (23 of 198) of MBC and were absent in other types of cancers. HER2 mutations were located in exon 15 and the in-frame insertions in exon 20 with corresponding region as did EGFR insertions. HER2 mutations were significantly more frequent in patient after the administration of trastuzumab (34.8 %, 8 of 23;P= 0.02). Mutations in exon 15 and 20 were more potent than wild-type HER2 in associating with activating signal transducers and inducing survival, invasiveness, and tumorigenicity.