胃腸道間質瘤c-kit基因突變的研究進展△_《中國普外基礎與臨床雜志》

作者：

何丹 ,  伍曉汀

四川大學華西醫院胃腸外科中心（四川成都 610041）;

關鍵詞：

胃腸腫瘤間質瘤基因突變

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　探討胃腸道間質瘤（gastrointestinal stromal tumor，GIST）c-kit基因突變特征與臨床病理、分子靶向治療及預后的相關性。
方法　采用文獻復習的方法，對研究胃腸道間質瘤分子遺傳學機理的相關文獻加以綜述。
結果　c-kit基因突變可能是GIST發生的早期事件，是GIST的普遍現象，不能作為GIST預后判斷的指標。然而，c-kit突變位點和方式是否影響GIST的生物學行為，能否作為評估預后的指標仍存在爭議。
結論　基因突變檢測對從分子水平上研究疾病、判斷預后以及指導用藥具有重要意義，需要不斷地深入研究。

引用本文： 何丹,伍曉汀. 胃腸道間質瘤c-kit基因突變的研究進展△. 中國普外基礎與臨床雜志, 2013, 20(7): 820-825. doi: 復制

1.	Nilsson B， Bumming P， Meis-Kindblom JM， et al. Gastrointestinal stromal tumors： the incidence， prevalence， clinical course， and prognostication in the preimatinib mesylate era—a population-based study in western Sweden[J]. Cancer， 2005， 103(4)：821-829.
2.	Mazur MT， Clark HB. Gastric stromal tumors. Reappraisal of histogenesis[J]. Am J Surg Pathol， 1983， 7(6)：507-519.
3.	Rubin BP. Gastrointestinal stromal tumours： an update[J]. Histopathology， 2006， 48(1)：83-96.
4.	Hirota S， Isozaki K， Moriyama Y， et al. Gain-of-function muta-tions of c-kit in human gastrointestinal stromal tumors[J]. Science，.
5.	Lux ML， Rubin BP， Biase TL， et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors[J]. Am J Pathol， 2000， 156(3)：791-795.
6.	Lasota J， Wozniak A， Sarlomo-Rikala M， et al. Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases[J]. Am J Pathol， 2000， 157(4)： 1091-1095.
7.	Corless CL， Barnett CM， Heinrich MC. Gastrointestinal stromal tumours： origin and molecular oncology[J]. Nat Rev Cancer， 2011， 11(12)： 865-878.
8.	Heinrich MC， Corless CL， Duensing A， et al. PDGFRA activ-ating mutations in gastrointestinal stromal tumors[J]. Science， 2003， 299(5607)： 708-710.
9.	Kang HJ， Nam SW， Kim H， et al. Correlation of KIT and platelet-derived growth factor receptor alpha mutations with gene activation and expression profiles in gastrointestinal stromal tumors[J]. Oncogene， 2005， 24(6)：1066-1074.
10.	Miettinen M， Fetsch JF， Sobin LH， et al. Gastrointestinal stromaltumors in patients with neurofibromatosis 1： a clinicopathologic and molecular genetic study of 45 cases[J]. Am J Surg Pathol， 2006， 30(1)： 90-96.
11.	Janeway KA， Kim SY， Lodish M， et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations[J]. Proc Natl Acad Sci U S A， 2011， 108(1)：314-318.
12.	Miettinen M， Wang ZF， Sarlomo-Rikala M， et al. Succinate dehydrogenase-deficient GISTs：a clinicopathologic， immunohistochemical， and molecular genetic study of 66 gastric GISTs with predilection to young age[J]. Am J Surg Pathol， 2011， 35(11)：1712-1721.
13.	Celestino R， Lima J， Faustino A， et al. Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors[J]. Eur J Hum Genet， 2012，[epub ahead of print].
14.	Du CY， Shi YQ， Zhou Y， et al. The analysis of status and clinicalimplication of KIT and PDGFRA mutations in gastrointestinal stromal tumor (GIST)[J]. J Surg Oncol， 2008， 98(3)：175-178.
15.	Corless CL， Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas[J]. Annu Rev Pathol， 2008， 3： 557-586.
16.	Lasota J， Corless CL， Heinrich MC， et al. Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations：a multicenter study on 54 cases[J]. Mod Pathol， 2008， 21(4)： 476-484.
17.	Corless CL， Schroeder A， Griffith D， et al. PDGFRA mutations in gastrointestinal stromal tumors： requency， spectrum and in vitro sensitivity to imatinib[J]. J Clin Oncol， 2005， 23(23)： 5357-5364.
18.	吳志勇，趙文毅，曹暉，等. c-kit基因突變對胃腸道間質瘤預后影響的薈萃分析[J]. 中華外科雜志， 2009， 47(11)：857-862.
19.	Lasota J， Jasinski M， Sarlomo-Rikala M， et al. Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas[J]. Am J Pathol， 1999， 154(1)：53-60.
20.	Taniguchi M， Nishida T， Hirota S， et al. Effect of c-kit mutationon prognosis of gastrointestinal stromal tumors[J]. Cancer Res， 1999， 59(17)：4297-4300.
21.	Debiec-Rychter M， Lasota J， Sarlomo-Rikala M， et al. Chromo-somal aberrations in malignant gastrointestinal stromal tumors： correlation with c-KIT gene mutation[J]. Cancer Genet Cytog-enet， 2001， 128(1)：24-30.
22.	Zheng S， Chen LR， Wang HJ， et al. Analysis of mutation and expression of c-kit and PDGFR-alpha gene in gastrointestinal stromal tumor[J]. Hepatogastroenterology， 2007， 54(80)：2285-2290.
23.	Tzen CY， Wang MN， Mau BL. Spectrum and prognostication of KIT and PDGFRA mutation in gastrointestinal stromal tumors[J]. Eur J Surg Oncol， 2008， 34(5)：563-568.
24.	Yamamoto H， Oda Y， Kawaguchi K， et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue)[J]. Am J Surg Pathol， 2004， 28(4)：479-488.
25.	Corless CL， Mcgreevey L， Haley A， et al. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeteror less in size[J]. Am J Pathol， 2002， 160(5)：1567-1572.
26.	侯英勇，朱雄增. 胃腸道間質瘤的分子生物學研究[J]. 腫瘤研究與臨床， 2006， 18(8)：507-512.
27.	Miettinen M， Makhlouf H， Sobin LH， et al. Gastrointestinal stromal tumors of the jejunum and ileum： a clinicopathologic， immunohistochemical， and molecular genetic study of 906 cases before imatinib with long-term follow-up[J]. Am J Surg Pathol， 2006， 30(4)：477-489.
28.	Lasota J， Vel D A， Wasag B， et al. Presence of homozygous KIT exon 11 mutations is strongly associated with malignant clinical behavior in gastrointestinal stromal tumors[J]. Lab Invest，.
29.	Andersson J， Bumming P， Meis-Kindblom JM， et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis[J]. Gastroenterology， 2006， 130(6)：1573-1581.
30.	Steigen SE， Eide TJ， Wasag B， et al. Mutations in gastrointestinal stromal tumors—a population-based study from Northern Norway[J]. APMIS， 2007， 115(4)：289-298.
31.	Hou YY， Grabellus F， Weber F， et al. Impact of KIT and PDGFRAgene mutations on prognosis of patients with gastrointestinal stromal tumors after complete primary tumor resection[J]. J Gastrointest Surg， 2009， 13(9)：1583-1592.
32.	Wozniak A， Rutkowski P， Piskorz A， et al. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST)： Polish Clinical GIST Registry experience[J]. Ann Oncol， 2012， 23(2)：353-360.
33.	Joensuu H， Roberts PJ， Sarlomo-Rikala M， et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor[J]. N Engl J Med， 2001， 344(14)：1052-1056.
34.	Heinrich MC， Corless CL， Demetri GD， et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor[J]. J Clin Oncol， 2003， 21(23)：4342-4349.
35.	Debiec-Rychter M， Dumez H， Judson I， et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromaltumours entered on phaseⅠandⅡstudies of the EORTC Soft Tissueand Bone Sarcoma Group[J]. Eur J Cancer， 2004， 40(5)：689-695.
36.	Heinrich MC， Owzar K， Corless CL， et al. Correlation of kinasegenotype and clinical outcome in the North American Intergroup PhaseⅢTrial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor：CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group[J]. J Clin Oncol， 2008， 26(33)：5360-5367.
37.	Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST).Comparison of two doses of imatinib for the treatment of unresec-table or metastatic gastrointestinal stromal tumors：a meta-analysisof 1 640 patients[J]. J Clin Oncol， 2010， 28(7)： 1247-1253.
38.	Casali PG， Blay JY. Gastrointestinal stromal tumours： ESMO Clinical Practice Guidelines for diagnosis， treatment and follow-up[J]. Ann Oncol， 2010， 21 Suppl 5：v98-v102.
39.	Blay JY， von Mehren M， Blackstein M E. Perspective on updatedtreatment guidelines for patients with gastrointestinal stromal tumors[J]. Cancer， 2010， 116(22)： 5126-5137.
40.	Yeh CN， Chen YY， Tseng JH， et al. Imatinib Mesylate forPatients with Recurrent or Metastatic Gastrointestinal StromalTumors Expressing KIT： A Decade Experience from Taiwan[J].Transl Oncol， 2011， 4(6)：328-335.
41.	Kim TW， Ryu M H， Lee H， et al. Kinase mutations and efficacyof imatinib in Korean patients with advanced gastrointestinal stromal tumors[J]. Oncologist， 2009， 14(5)：540-547.
42.	Yeh CN， Chen TW， Lee HL， et al. Kinase mutations and imatinibmesylate response for 64 Taiwanese with advanced GIST： prelim-inary experience from Chang Gung Memorial Hospital[J]. Ann Surg Oncol， 2007， 14(3)：1123-1128.
43.	Kang HJ， Ryu MH， Kim KM， et al. Imatinib efficacy by tumorgenotype in Korean patients with advanced gastrointestinal stromaltumors (GIST)： The Korean GIST Study Group (KGSG) study[J]. Acta Oncol， 2012， 51(4)：528-536.
44.	Demetri GD， Wang Y， Wehrle E， et al. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors[J]. J Clin Oncol， 2009， 27(19)：3141-3147.
45.	Nishida T， Kanda T， Nishitani A， et al. Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor[J]. Cancer Sci， 2008， 99(4)：799-804.
46.	Heinrich MC， Maki RG， Corless CL， et al. Primary and secon-dary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor[J]. J Clin Oncol， 2008， 26(33)：5352-5359.
47.	Rutkowski P， Bylina E， Klimczak A， et al. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinalstromal tumors (GIST) after imatinib failure—one institution study[J]. BMC Cancer， 2012， 12：107.
48.	Yoon DH， Ryu MH， Ryoo BY， et al. Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib： relationship between efficacy and tumor genotype in Korean patients[J]. Invest New Drugs， 2012， 30 (2)：819-827.
49.	Chen YY， Yeh CN， Cheng CT， et al. Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance[J]. World J Gastroenterol， 2011， 17 (16)：2113-2119.
50.	Prenen H， Cools J， Mentens N， et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate[J]. Clin Cancer Res， 2006， 12(8)：2622-2627.
51.	， 279(5350)： 577-580.
52.	， 87(10)：1029-1041.

1. Nilsson B， Bumming P， Meis-Kindblom JM， et al. Gastrointestinal stromal tumors： the incidence， prevalence， clinical course， and prognostication in the preimatinib mesylate era—a population-based study in western Sweden[J]. Cancer， 2005， 103(4)：821-829.
2. Mazur MT， Clark HB. Gastric stromal tumors. Reappraisal of histogenesis[J]. Am J Surg Pathol， 1983， 7(6)：507-519.
3. Rubin BP. Gastrointestinal stromal tumours： an update[J]. Histopathology， 2006， 48(1)：83-96.
4. Hirota S， Isozaki K， Moriyama Y， et al. Gain-of-function muta-tions of c-kit in human gastrointestinal stromal tumors[J]. Science，.
5. Lux ML， Rubin BP， Biase TL， et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors[J]. Am J Pathol， 2000， 156(3)：791-795.
6. Lasota J， Wozniak A， Sarlomo-Rikala M， et al. Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases[J]. Am J Pathol， 2000， 157(4)： 1091-1095.
7. Corless CL， Barnett CM， Heinrich MC. Gastrointestinal stromal tumours： origin and molecular oncology[J]. Nat Rev Cancer， 2011， 11(12)： 865-878.
8. Heinrich MC， Corless CL， Duensing A， et al. PDGFRA activ-ating mutations in gastrointestinal stromal tumors[J]. Science， 2003， 299(5607)： 708-710.
9. Kang HJ， Nam SW， Kim H， et al. Correlation of KIT and platelet-derived growth factor receptor alpha mutations with gene activation and expression profiles in gastrointestinal stromal tumors[J]. Oncogene， 2005， 24(6)：1066-1074.
10. Miettinen M， Fetsch JF， Sobin LH， et al. Gastrointestinal stromaltumors in patients with neurofibromatosis 1： a clinicopathologic and molecular genetic study of 45 cases[J]. Am J Surg Pathol， 2006， 30(1)： 90-96.
11. Janeway KA， Kim SY， Lodish M， et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations[J]. Proc Natl Acad Sci U S A， 2011， 108(1)：314-318.
12. Miettinen M， Wang ZF， Sarlomo-Rikala M， et al. Succinate dehydrogenase-deficient GISTs：a clinicopathologic， immunohistochemical， and molecular genetic study of 66 gastric GISTs with predilection to young age[J]. Am J Surg Pathol， 2011， 35(11)：1712-1721.
13. Celestino R， Lima J， Faustino A， et al. Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors[J]. Eur J Hum Genet， 2012，[epub ahead of print].
14. Du CY， Shi YQ， Zhou Y， et al. The analysis of status and clinicalimplication of KIT and PDGFRA mutations in gastrointestinal stromal tumor (GIST)[J]. J Surg Oncol， 2008， 98(3)：175-178.
15. Corless CL， Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas[J]. Annu Rev Pathol， 2008， 3： 557-586.
16. Lasota J， Corless CL， Heinrich MC， et al. Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations：a multicenter study on 54 cases[J]. Mod Pathol， 2008， 21(4)： 476-484.
17. Corless CL， Schroeder A， Griffith D， et al. PDGFRA mutations in gastrointestinal stromal tumors： requency， spectrum and in vitro sensitivity to imatinib[J]. J Clin Oncol， 2005， 23(23)： 5357-5364.
18. 吳志勇，趙文毅，曹暉，等. c-kit基因突變對胃腸道間質瘤預后影響的薈萃分析[J]. 中華外科雜志， 2009， 47(11)：857-862.
19. Lasota J， Jasinski M， Sarlomo-Rikala M， et al. Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas[J]. Am J Pathol， 1999， 154(1)：53-60.
20. Taniguchi M， Nishida T， Hirota S， et al. Effect of c-kit mutationon prognosis of gastrointestinal stromal tumors[J]. Cancer Res， 1999， 59(17)：4297-4300.
21. Debiec-Rychter M， Lasota J， Sarlomo-Rikala M， et al. Chromo-somal aberrations in malignant gastrointestinal stromal tumors： correlation with c-KIT gene mutation[J]. Cancer Genet Cytog-enet， 2001， 128(1)：24-30.
22. Zheng S， Chen LR， Wang HJ， et al. Analysis of mutation and expression of c-kit and PDGFR-alpha gene in gastrointestinal stromal tumor[J]. Hepatogastroenterology， 2007， 54(80)：2285-2290.
23. Tzen CY， Wang MN， Mau BL. Spectrum and prognostication of KIT and PDGFRA mutation in gastrointestinal stromal tumors[J]. Eur J Surg Oncol， 2008， 34(5)：563-568.
24. Yamamoto H， Oda Y， Kawaguchi K， et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue)[J]. Am J Surg Pathol， 2004， 28(4)：479-488.
25. Corless CL， Mcgreevey L， Haley A， et al. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeteror less in size[J]. Am J Pathol， 2002， 160(5)：1567-1572.
26. 侯英勇，朱雄增. 胃腸道間質瘤的分子生物學研究[J]. 腫瘤研究與臨床， 2006， 18(8)：507-512.
27. Miettinen M， Makhlouf H， Sobin LH， et al. Gastrointestinal stromal tumors of the jejunum and ileum： a clinicopathologic， immunohistochemical， and molecular genetic study of 906 cases before imatinib with long-term follow-up[J]. Am J Surg Pathol， 2006， 30(4)：477-489.
28. Lasota J， Vel D A， Wasag B， et al. Presence of homozygous KIT exon 11 mutations is strongly associated with malignant clinical behavior in gastrointestinal stromal tumors[J]. Lab Invest，.
29. Andersson J， Bumming P， Meis-Kindblom JM， et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis[J]. Gastroenterology， 2006， 130(6)：1573-1581.
30. Steigen SE， Eide TJ， Wasag B， et al. Mutations in gastrointestinal stromal tumors—a population-based study from Northern Norway[J]. APMIS， 2007， 115(4)：289-298.
31. Hou YY， Grabellus F， Weber F， et al. Impact of KIT and PDGFRAgene mutations on prognosis of patients with gastrointestinal stromal tumors after complete primary tumor resection[J]. J Gastrointest Surg， 2009， 13(9)：1583-1592.
32. Wozniak A， Rutkowski P， Piskorz A， et al. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST)： Polish Clinical GIST Registry experience[J]. Ann Oncol， 2012， 23(2)：353-360.
33. Joensuu H， Roberts PJ， Sarlomo-Rikala M， et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor[J]. N Engl J Med， 2001， 344(14)：1052-1056.
34. Heinrich MC， Corless CL， Demetri GD， et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor[J]. J Clin Oncol， 2003， 21(23)：4342-4349.
35. Debiec-Rychter M， Dumez H， Judson I， et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromaltumours entered on phaseⅠandⅡstudies of the EORTC Soft Tissueand Bone Sarcoma Group[J]. Eur J Cancer， 2004， 40(5)：689-695.
36. Heinrich MC， Owzar K， Corless CL， et al. Correlation of kinasegenotype and clinical outcome in the North American Intergroup PhaseⅢTrial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor：CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group[J]. J Clin Oncol， 2008， 26(33)：5360-5367.
37. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST).Comparison of two doses of imatinib for the treatment of unresec-table or metastatic gastrointestinal stromal tumors：a meta-analysisof 1 640 patients[J]. J Clin Oncol， 2010， 28(7)： 1247-1253.
38. Casali PG， Blay JY. Gastrointestinal stromal tumours： ESMO Clinical Practice Guidelines for diagnosis， treatment and follow-up[J]. Ann Oncol， 2010， 21 Suppl 5：v98-v102.
39. Blay JY， von Mehren M， Blackstein M E. Perspective on updatedtreatment guidelines for patients with gastrointestinal stromal tumors[J]. Cancer， 2010， 116(22)： 5126-5137.
40. Yeh CN， Chen YY， Tseng JH， et al. Imatinib Mesylate forPatients with Recurrent or Metastatic Gastrointestinal StromalTumors Expressing KIT： A Decade Experience from Taiwan[J].Transl Oncol， 2011， 4(6)：328-335.
41. Kim TW， Ryu M H， Lee H， et al. Kinase mutations and efficacyof imatinib in Korean patients with advanced gastrointestinal stromal tumors[J]. Oncologist， 2009， 14(5)：540-547.
42. Yeh CN， Chen TW， Lee HL， et al. Kinase mutations and imatinibmesylate response for 64 Taiwanese with advanced GIST： prelim-inary experience from Chang Gung Memorial Hospital[J]. Ann Surg Oncol， 2007， 14(3)：1123-1128.
43. Kang HJ， Ryu MH， Kim KM， et al. Imatinib efficacy by tumorgenotype in Korean patients with advanced gastrointestinal stromaltumors (GIST)： The Korean GIST Study Group (KGSG) study[J]. Acta Oncol， 2012， 51(4)：528-536.
44. Demetri GD， Wang Y， Wehrle E， et al. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors[J]. J Clin Oncol， 2009， 27(19)：3141-3147.
45. Nishida T， Kanda T， Nishitani A， et al. Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor[J]. Cancer Sci， 2008， 99(4)：799-804.
46. Heinrich MC， Maki RG， Corless CL， et al. Primary and secon-dary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor[J]. J Clin Oncol， 2008， 26(33)：5352-5359.
47. Rutkowski P， Bylina E， Klimczak A， et al. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinalstromal tumors (GIST) after imatinib failure—one institution study[J]. BMC Cancer， 2012， 12：107.
48. Yoon DH， Ryu MH， Ryoo BY， et al. Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib： relationship between efficacy and tumor genotype in Korean patients[J]. Invest New Drugs， 2012， 30 (2)：819-827.
49. Chen YY， Yeh CN， Cheng CT， et al. Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance[J]. World J Gastroenterol， 2011， 17 (16)：2113-2119.
50. Prenen H， Cools J， Mentens N， et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate[J]. Clin Cancer Res， 2006， 12(8)：2622-2627.
51. ， 279(5350)： 577-580.
52. ， 87(10)：1029-1041.

《中國普外基礎與臨床雜志》

胃腸道間質瘤c-kit基因突變的研究進展△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

《中國普外基礎與臨床雜志》

胃腸道間質瘤c-kit基因突變的研究進展△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料