Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review

被引:3
|
作者
Ge, Qichao [1 ,2 ]
Liu, Yang [1 ,2 ]
Yang, Fan [1 ]
Sun, Guangwei [3 ]
Guo, Jintao [1 ]
Sun, Siyu [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Gastroenterol, 36 Sanhao St, Shenyang 110004, Peoples R China
[2] China Med Univ, Innovat Res Ctr Integrated Canc Om, Shengjing Hosp, Shenyang 110004, Peoples R China
[3] China Med Univ, Shengjing Hosp, Innovat Engn Technol Res Ctr Cell Therapy, Shenyang 110022, Peoples R China
基金
中国国家自然科学基金;
关键词
gastrointestinal stromal tumor; whole-exome sequencing; germline mutation; familial disease; precision oncology; GERMLINE MUTATION; KIT; SUNITINIB; IMATINIB; REGORAFENIB; MULTICENTER; EFFICACY; FAILURE; SAFETY; GENE;
D O I
10.3390/ijms24010830
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subepithelial lesions accompanied by cutaneous hyperpigmentation, which were subsequently diagnosed as multinodular GISTs. Endoscopic surgery was initially conducted to remove the larger lesions, and pathological examinations were then conducted for the diagnosis of GISTs. Family history revealed that some other family members had similar cutaneous pigmentations. Whole-exome sequencing was used to search for potential driver mutations, and Sanger sequencing was used for mutation validation. A novel primary driver mutation of KIT (c.G2485C, p.A829P) was detected in these hereditary GISTs, which has been reported in some targeted chemotherapy-resistant GISTs. Cell models were subsequently established for the rapid screening of candidate drugs and exploring potential mechanisms. This mutation could lead to cell proliferation and imatinib resistance by ligand-independent activation of KIT; however, ripretinib administration was identified as an applicable targeted therapy for this mutation. The mutation activated the JAK/STAT3 and MAPK/ERK pathways, which could be inhibited by ripretinib administration. To the best of our knowledge, this is the first report of the KIT-A829P mutation in familial GISTs, complementing the pathogenesis of familial GISTs and providing valuable information for the precision treatment of this disease.
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页数:13
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