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KIF5B gene and RET gene fusion gene and method for determining the effectiveness of cancer treatment targeting the fusion gene

机译:KIF5B基因和RET基因融合基因以及确定针对该融合基因的癌症治疗效果的方法

摘要

In order to identify a gene that can serve as an indicator for predicting the effectiveness of a drug treatment of cancer and to provide a novel method for predicting the effectiveness of a drug treatment targeting said gene, lung adenocarcinomas were subjected to whole-transcriptome sequencing. As a result, in-frame fusion transcripts between the KIF5B gene and the RET gene were identified. The KIF5B-RET gene fusions were detected in 6 out of 319 (2%) LADC specimens from Japanese individuals and 1 out of 80 (1%) LADC specimens from U.S.A. individuals. None of the seven subjects revealed known activating mutations such as EGFR, KRAS or ALK oncogenes; thus, said gene fusions were found to be responsible mutations (driver mutations) for oncogenesis. Since said gene fusions are considered to induce constitutive activation of RET tyrosine kinase protein, it was found that treatments with RET tyrosine kinase inhibitors are effective in patients with detection of said gene fusions.
机译:为了鉴定可用作预测癌症药物治疗效果的指标的基因并提供预测针对所述基因的药物治疗效果的新方法,对肺腺癌进行了全转录组测序。结果,鉴定了KIF5B基因和RET基因之间的框内融合转录物。在来自日本个人的319个(2%)LADC标本中有6个检测到了KIF5B-RET基因融合体,来自美国的80个(1%)的LADC标本中有1个检测到了KIF5B-RET基因融合体。七个受试者中没有一个发现已知的激活突变,例如EGFR,KRAS或ALK癌基因。因此,发现所述基因融合体是致癌作用的负责突变(驱动子突变)。由于所述基因融合被认为诱导RET酪氨酸激酶蛋白的组成性活化,因此发现用RET酪氨酸激酶抑制剂的治疗在检测所述基因融合的患者中是有效的。

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