KIT基因双突变在胃肠道间质瘤中的作用
| 作者: |
1孟琳,
2张声
1 福建医科大学附属第一医院病理科，福州 350005 2 福建医科大学基础医学院病理学系，福州 350005 |
| 通讯: | |
| DOI: | 10.3978/j.issn.2095-6959.2018.04.024 |
| 基金: | 福建省自然科学基金(2015J01452)。 |
摘要
胃肠道间质瘤(gastrointestinal stromal tumors，GISTs)是胃肠道最常见的间叶源性肿瘤，KIT/PDGFRA基因是其驱动基因，伊马替尼是GISTs的一线靶向药物。长期靶向药物治疗GISTs常发生复发、耐药和转移，分子测序发现存在KIT基因双突变。GISTs中KIT或PDGFRA双突变率约为61.3%，多数研究提示双突变抑制伊马替尼与ATP区的结合，激活下游增殖通路，引起耐药及肿瘤转移；但也有文献提示KIT/PDGFRA基因双突变对伊马替尼更敏感或阻滞肿瘤的生长，表现出双相作用。
关键词：
KIT基因；双突变；胃肠道间质瘤
Role of KIT gene double mutation in gastrointestinal stromal tumors
DOI: 10.3978/j.issn.2095-6959.2018.04.024
Foundation: This work was supported by Fujian Provincial Natural Science Foundation, China (2015J01452).
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The KIT/PDGFRA gene is the driver gene, and imatinib is a first-line target drug for GISTs. Relapse, drug resistance and metastasis of GISTs often occur in the long-term treatment of target drug. Molecule sequencing shows the double mutation in KIT gene. The double mutation of KIT or PDGFRA in GISTs is about 61.3%. The results of most studies suggest that double mutation of KIT gene inhibits the combination of imatinib and ATP domain of KIT, which activates the proliferation pathways in downstream, and causes the drug resistance and tumor metastasis. However, there are opposite conclusions that double mutation of KIT/PDGFRA gene is more sensitive to imatinib or blocks the growth of GISTs. These results shows that the double mutation of KIT gene has double phase effect on GISTs.
Keywords：
KIT gene; double mutation; gastrointestinal stromal tumor