Gastrointestinal stromal tumors: What do we know now?

Modern Pathology

Volumn 27, Issue SUPPL. 1, 2014, Pages

  Corless, Christopher L ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

GIST; KIT; PDGFRA

Indexed keywords

B RAF KINASE; DESMIN; IMATINIB; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN KINASE B; PROTEIN TYROSINE KINASE INHIBITOR; REGORAFENIB; SMOOTH MUSCLE ACTIN; STAT3 PROTEIN; STEM CELL FACTOR; SUCCINATE DEHYDROGENASE; SUNITINIB; TRANSCRIPTION FACTOR ER81; STEM CELL FACTOR RECEPTOR;

ARTICLE; CANCER GROWTH; CANCER PROGNOSIS; CANCER RESISTANCE; CLINICAL FEATURE; DRUG EFFICACY; EXON; GASTROINTESTINAL STROMAL TUMOR; GENE DELETION; GENE EXPRESSION; GENE INSERTION; GENOTYPE; INTERSTITIAL CELL OF CAJAL; LIVER METASTASIS; POINT MUTATION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; TREATMENT RESPONSE; WILD TYPE; BRAF GENE; CARCINOGENESIS; GENE ACTIVATION; GERMLINE MUTATION; HUMAN; KIT GENE; META ANALYSIS (TOPIC); NONHUMAN; OVERALL SURVIVAL; PDGFRA GENE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROSPECTIVE STUDY; SDHA GENE; SDHB GENE; SDHC GENE; SOMATIC MUTATION; TREATMENT OUTCOME; TUMOR GROWTH; TUMOR RECURRENCE;

ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; GASTROINTESTINAL STROMAL TUMORS; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HUMANS; INDIVIDUALIZED MEDICINE; MOLECULAR TARGETED THERAPY; MUTATION; PATIENT SELECTION; PHENOTYPE; PREDICTIVE VALUE OF TESTS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-KIT; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA; TUMOR MARKERS, BIOLOGICAL;

EID: 84891695832     PISSN: 08933952     EISSN: 15300285     Source Type: Journal    
DOI: 10.1038/modpathol.2013.173     Document Type: Article

References (150)

1. Chan KH, Chan CW, Chow WH, et al. Gastrointestinal stromal tumors in a cohort of Chinese patients in Hong Kong. World J Gastroenterol 2006;12: 2223-2228.
2. Goettsch WG, Bos SD, Breekveldt-Postma N, et al. Incidence of gastrointestinal stromal tumours is underestimated: Results of a nation-wide study. Eur J Cancer 2005;41:2868-2872. (Pubitemid 41713125)
3. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. Cancer 2005;103:821-829. (Pubitemid 40216412)
4. Tryggvason G, Gislason HG, Magnusson MK, et al. Gastrointestinal stromal tumors in Iceland, 1990-2003: the Icelandic GIST study, a populationbased incidence and pathologic risk stratification study. Int J Cancer 2005;117:289-293. (Pubitemid 41377450)
5. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004;22: 3813-3825. (Pubitemid 41095223)
6. Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol 2003;54:3-24. (Pubitemid 36604461)
7. Hirota S, Isozaki K, Moriyama Y, et al. Gain-offunction mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-580. (Pubitemid 28067289)
8. Kindblom LG, Remotti HE, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998;152:1259-1269. (Pubitemid 28221878)
9. West RB, Corless CL, Chen X, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165: 107-113. (Pubitemid 38821818)
10. Janeway KA, Kim SY, Lodish M, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci USA 2011;108:314-318.
11. Hanks SK, Quinn AM, Hunter T. The protein kinase family: Conserved features and deduced phylogeny of the catalytic domains. Science 1988;241:42-52.
12. Ernst SI, Hubbs AE, Przygodzki RM, et al. KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors. Lab Invest 1998;78: 1633-1636. (Pubitemid 29022239)
13. 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. Am J Pathol 1999;154:53-60. (Pubitemid 29031611)
14. Singer S, Rubin BP, Lux ML, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol 2002;20:3898-3905.
15. Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 1999;59:4297-4300. (Pubitemid 29418746)
16. Andersson J, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 2006;130:1573-1581. (Pubitemid 43668833)
17. Cho S, Kitadai Y, Yoshida S, et al. Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach. Int J Oncol 2006;28: 1361-1367.
18. Liu XH, Bai CG, Xie Q, et al. Prognostic value of KIT mutation in gastrointestinal stromal tumors. World J Gastroenterol 2005;11:3948-3952. (Pubitemid 41025255)
19. Martin J, Poveda A, Llombart-Bosch A, et al. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol 2005;23:6190-6198.
20. Tzen CY, Mau BL. Analysis of CD117-negative gastrointestinal stromal tumors. World J Gastroenterol 2005;11:1052-1055.
21. Wardelmann E, Losen I, Hans V, et al. Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer 2003;106:887-895. (Pubitemid 37071667)
22. Lux ML, Rubin BP, Biase TL, et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 2000;156: 791-795. (Pubitemid 30626936)
23. 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. Mod Pathol 2008;21:476-484. (Pubitemid 351441037)
24. Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 2001;61:8118-8121. (Pubitemid 33091601)
25. Heinrich MC, Griffith DJ, Druker BJ, et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000;96: 925-932. (Pubitemid 30618049)
26. Sommer G, Agosti V, Ehlers I, et al. Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proc Natl Acad Sci USA 2003;100:6706-6711. (Pubitemid 36666644)
27. Rubin BP, Antonescu CR, Scott-Browne JP, et al. A knock-in mouse model of gastrointestinal stromal tumor harboring kit K641E. Cancer Res 2005;65: 6631-6639. (Pubitemid 41060699)
28. Chen H, Hirota S, Isozaki K, et al. Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumours. Gut 2002;51:793-796. (Pubitemid 35408597)
29. O'riain C, Corless CL, Heinrich MC, et al. Gastrointestinal stromal tumors: insights from a new familial GIST kindred with unusual genetic and pathologic features. Am J Surg Pathol 2005;29: 1680-1683.
30. Duensing A, Medeiros F, McConarty B, et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene 2004;23:3999-4006. (Pubitemid 38747928)
31. Rossi F, Ehlers I, Agosti V, et al. Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor. Proc Natl Acad Sci USA 2006;103:12843-12848. (Pubitemid 44298649)
32. Duensing A, Joseph N, Liu C, et al. Protein kinase C theta (PKC{theta}) is selectively expressed and constitutively phosphorylatedd in gastrointestinal stromal tumors (GISTs). AACR Meet Abstr 2004; 2004:708.
33. Chi P, Chen Y, Zhang L, et al. ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours. Nature 2010;467: 849-853.
34. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21:4342-4349. (Pubitemid 46621810)
35. Antonescu CR, Besmer P, Guo T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 2005;11:4182-4190. (Pubitemid 40791584)
36. Chen LL, Holden JA, Choi H, et al. Evolution from heterozygous to homozygous KIT mutation in gastrointestinal stromal tumor correlates with the mechanism of mitotic nondisjunction and significant tumor progression. Mod Pathol 2008;21:826-836. (Pubitemid 351896656)
37. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003;299:708-710. (Pubitemid 36159485)
38. Hirota S, Ohashi A, Nishida T, et al. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 2003;125:660-667. (Pubitemid 37070684)
39. 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. Oncogene 2005;24:1066-1074. (Pubitemid 40313883)
40. Matei D, Satpathy M, Cao L, et al. The plateletderived growth factor receptor alpha is destabilized by geldanamycins in cancer cells. J Biol Chem 2007;282:445-453. (Pubitemid 47076653)
41. Debiec-Rychter M, Wasag B, Stul M, et al. Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. J Pathol 2004;202: 430-438. (Pubitemid 38456161)
42. Duensing A, Joseph NE, Medeiros F, et al. Protein kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs). Cancer Res 2004;64:5127-5131. (Pubitemid 39006529)
43. Wozniak A, Sciot R, Guillou L, et al. Array CGH analysis in primary gastrointestinal stromal tumors: cytogenetic profile correlates with anatomic site and tumor aggressiveness, irrespective of mutational status. Genes Chromosomes Cancer 2007;46:261-276. (Pubitemid 46155321)
44. Subramanian S, West RB, Corless CL, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene 2004;23:7780-7790. (Pubitemid 39457028)
45. Wasag B, Debiec-Rychter M, Pauwels P, et al. Differential expression of KIT/PDGFRA mutant isoforms in epithelioid and mixed variants of gastrointestinal stromal tumors depends predominantly on the tumor site. Mod Pathol 2004;17:889-894. (Pubitemid 38993772)
46. Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 2004;28:889-894. (Pubitemid 38856844)
47. Sakurai S, Hasegawa T, Sakuma Y, et al. Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: a subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene. Hum Pathol 2004;35:1223-1230. (Pubitemid 39361645)
48. Wardelmann E, Hrychyk A, Merkelbach-Bruse S, et al. Association of platelet-derived growth factor receptor alpha mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors. J Mol Diagn 2004;6: 197-204. (Pubitemid 39136646)
49. Lasota J, Dansonka-Mieszkowska A, Sobin LH, et al. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 2004;84:874-883. (Pubitemid 38833247)
50. Hostein I, Faur N, Primois C, et al. BRAF mutation status in gastrointestinal stromal tumors. Am J Clin Pathol 2010;133:141-148.
51. Andersson J, Sihto H, Meis-Kindblom JM, et al. NF1-associated gastrointestinal stromal tumors have unique clinical, phenotypic, and genotypic characteristics. Am J Surg Pathol 2005;29:1170-1176. (Pubitemid 41232989)
52. de Raedt T, Cools J, Debiec-Rychter M, et al. Intestinal neurofibromatosis is a subtype of familial GIST and results from a dominant activating mutation in PDGFRA. Gastroenterology 2006;131:1907-1912. (Pubitemid 44958505)
53. Kang DY, Park CK, Choi JS, et al. Multiple gastrointestinal stromal tumors: clinicopathologic and genetic analysis of 12 patients. Am J Surg Pathol 2007;31:224-232. (Pubitemid 46175023)
54. Maertens O, Prenen H, Debiec-Rychter M, et al. Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet 2006;15:1015-1023. (Pubitemid 43338241)
55. Miettinen M, Fetsch JF, Sobin LH, et al. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 2006;30: 90-96. (Pubitemid 43740214)
56. Stewart C, Corless C, Rubin BP, et al. Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumours in neurofibromatosis type 1. J Med Genet 2007;44:e61.
57. Kinoshita K, Hirota S, Isozaki K, et al. Absence of c-kit gene mutations in gastrointestinal stromal tumours from neurofibromatosis type 1 patients. J Pathol 2004;202:80-85. (Pubitemid 38072848)
58. Miettinen M, Killian JK, Wang ZF, et al. Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation. Am J Surg Pathol 2012;37:234-240.
59. Mason E, Hornick JL. Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine production in gastrointestinal stromal tumors: implications for mechanisms of tumorigenesis. Mod Pathol; advance online publication, 7 June 2013 (e-pub ahead of print).
60. Killian JK, Kim SY, Miettinen M, et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov 2013;3:648-657.
61. Pantaleo MA, Astolfi A, Indio V, et al. SDHA loss-offunction mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. J Natl Cancer Inst 2011;103:983-987.
62. Wagner AJ, Remillard SP, Zhang YX, et al. Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. Mod Pathol 2013;26:289-294.
63. Dwight T, Benn DE, Clarkson A, et al. Loss of SDHA expression identifies SDHA mutations in succinate dehydrogenase-deficient gastrointestinal stromal tumors. Am J Surg Pathol 2012;37:226-233.
64. Pantaleo MA, Astolfi A, Urbini M, et al. Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST. Eur J Hum Genet 2013 (e-pub ahead of print).
65. Oudijk L, Gaal J, Korpershoek E, et al. SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors. Mod Pathol 2013;3:456-463.
66. Italiano A, Chen CL, Sung YS, et al. SDHA loss of function mutations in a subset of young adult wildtype gastrointestinal stromal tumors. BMC Cancer 2012;14:408.
67. Belinsky MG, Rink L, Flieder DB, et al. Overexpression of insulin-like growth factor 1 receptor and frequent mutational inactivation of SDHA in wildtype SDHB-negative gastrointestinal stromal tumors. Genes Chromosomes Cancer 2013;52:214-224.
68. Nannini M, Astolfi A, Paterini P, et al. Expression of IGF-1 receptor in KIT/PDGF receptor-a wild-type gastrointestinal stromal tumors with succinate dehydrogenase complex dysfunction. Future Oncol 2013;9:121-126.
69. Prakash S, Sarran L, Socci N, et al. Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol 2005;27:179-187. (Pubitemid 40604837)
70. Janeway KA, Liegl B, Harlow A, et al. Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res 2007;67:9084-9088. (Pubitemid 47535893)
71. Agaram NP, LaQuaglia MP, Ustun B, et al. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res 2008;14:3204-3215.
72. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney Triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc 1999;74:543-552.
73. Beghini A, Tibiletti MG, Roversi G, et al. Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa. Cancer 2001;92: 657-662. (Pubitemid 32735203)
74. Chompret A, Kannengiesser C, Barrois M, et al. PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology 2004;126:318-321. (Pubitemid 38040746)
75. Hirota S, Nishida T, Isozaki K, et al. Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene. Gastroenterology 2002;122:1493-1499. (Pubitemid 34465189)
76. Isozaki K, Terris B, Belghiti J, et al. Germlineactivating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors. Am J Pathol 2000;157:1581-1585.
77. Maeyama H, Hidaka E, Ota H, et al. Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene. Gastroenterology 2001;120:210-215. (Pubitemid 32061885)
78. Nishida T, Hirota S, Taniguchi M, et al. Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 1998;19:323-324. (Pubitemid 28357901)
79. Agaimy A, Wunsch PH, Hofstaedter F, et al. Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol 2007;31:113-120. (Pubitemid 46036910)
80. Corless CL, McGreevey L, Haley A, et al. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 2002;160:1567-1572. (Pubitemid 34525636)
81. Kawanowa K, Sakuma Y, Sakurai S, et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol 2006;37: 1527-1535. (Pubitemid 44792229)
82. Muenst S, Thies S, Went P, et al. Frequency, phenotype, and genotype of minute gastrointestinal stromal tumors in the stomach: an autopsy study. Hum Pathol 2011;42:1849-1854.
83. Rossi S, Gasparotto D, Toffolatti L, et al. Molecular and clinicopathologic characterization of gastrointestinal stromal tumors (GISTs) of small size. Am J Surg Pathol 2010;34:1480-1491.
84. Gasparotto D, Rossi S, Bearzi I, et al. Multiple primary sporadic gastrointestinal stromal tumors in the adult: an underestimated entity. Clin Cancer Res 2008;14:5715-5721.
85. Bergmann F, Gunawan B, Hermanns B, et al. Cytogenetic and morphologic characteristics of gastrointestinal stromal tumors. Recurrent rearrangement of chromosome 1 and losses of chromosomes 14 and 22 as common anomalies. Verh Dtsch Ges Pathol 1998;82:275-278.
86. Debiec-Rychter M, Lasota J, Sarlomo-Rikala M, et al. Chromosomal aberrations in malignant gastrointestinal stromal tumors: correlation with c-KIT gene mutation. Cancer Genet Cytogenet 2001;128:24-30. (Pubitemid 32655477)
87. Fukasawa T, Chong JM, Sakurai S, et al. Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor. Jpn J Cancer Res 2000;91:1241-1249. (Pubitemid 32042358)
88. Heinrich MC, Rubin BP, Longley BJ, et al. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 2002;33:484-495. (Pubitemid 34747867)
89. Kim NG, Kim JJ, Ahn JY, et al. Putative chromosomal deletions on 9P, 9Q and 22Q occur preferentially in malignant gastrointestinal stromal tumors. Int J Cancer 2000;85:633-638. (Pubitemid 30080474)
90. Assamaki R, Sarlomo-Rikala M, Lopez-Guerrero JA, et al. Array comparative genomic hybridization analysis of chromosomal imbalances and their target genes in gastrointestinal stromal tumors. Genes Chromosomes Cancer 2007;46:564-576. (Pubitemid 46649571)
91. Gunawan B, von HA, Sander B, et al. An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications. J Pathol 2007;211:463-470. (Pubitemid 46332558)
92. El Rifai W, Sarlomo-Rikala M, Miettinen M, et al. DNA copy number losses in chromosome 14: an early change in gastrointestinal stromal tumors. Cancer Res 1996;56:3230-3233. (Pubitemid 26242968)
93. O'Leary T, Ernst S, Przygodzki R, et al. Loss of heterozygosity at 1p36 predicts poor prognosis in gastrointestinal stromal/smooth muscle tumors. Lab Invest 1999;79:1461-1467. (Pubitemid 30013911)
94. Schurr P, Wolter S, Kaifi J, et al. Microsatellite DNA alterations of gastrointestinal stromal tumors are predictive for outcome. Clin Cancer Res 2006;12: 5151-5157. (Pubitemid 44453343)
95. el-Rifai W, Sarlomo-Rikala M, Andersson LC, et al. High-resolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci. Genes Chromosomes Cancer 2000;27:387-391. (Pubitemid 30127627)
96. Yamamoto H, Tobo T, Nakamori M, et al. Neurofibromatosis type 1-related gastrointestinal stromal tumors: a special reference to loss of heterozygosity at 14q and 22q. J Cancer Res Clin Oncol 2009;135: 791-798.
97. Hur K, Lee HJ,Woo JH, et al. Gene expression profiling of human gastrointestinal stromal tumors according to its malignant potential. Dig Dis Sci 2010;55: 2561-2567.
98. Perrone F, Tamborini E, Dagrada GP, et al. 9p21 locus analysis in high-risk gastrointestinal stromal tumors characterized for c-kit and platelet-derived growth factor receptor alpha gene alterations. Cancer 2005;104:159-169. (Pubitemid 40847764)
99. Ricci R, Arena V, Castri F, et al. Role of p16/INK4a in gastrointestinal stromal tumor progression. Am J Clin Pathol 2004;122:35-43. (Pubitemid 38849870)
100. Sabah M, Cummins R, Leader M, et al. Loss of heterozygosity of chromosome 9p and loss of p16INK4A expression are associated with malignant gastrointestinal stromal tumors. Mod Pathol 2004;17:1364-1371. (Pubitemid 39472991)
101. Schneider-Stock R, Boltze C, Lasota J, et al. Loss of p16 protein defines high-risk patients with gastrointestinal stromal tumors: a tissue microarray study. Clin Cancer Res 2005;11(2 Pt 1): 638-645. (Pubitemid 40116890)
102. Feakins RM. The expression of p53 and bcl-2 in gastrointestinal stromal tumours is associated with anatomical site, and p53 expression is associated with grade and clinical outcome. Histopathology 2005;46:270-279. (Pubitemid 40343173)
103. Panizo-Santos A, Sola I, Vega F, et al. Predicting metastatic risk of gastrointestinal stromal tumors: role of cell proliferation and cell cycle regulatory proteins. Int J Surg Pathol 2000;8:133-144. (Pubitemid 30413909)
104. Romeo S, Debiec-Rychter M, Van Glabbeke M, et al. Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res 2009;15:4198.
105. Tornillo L, Duchini G, Carafa V, et al. Patterns of gene amplification in gastrointestinal stromal tumors (GIST). Lab Invest 2005;85:921-931. (Pubitemid 41021300)
106. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561-566.
107. 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. N Engl J Med 2001;344:1052-1056. (Pubitemid 32267975)
108. Van Oosterom AT, Judson I, Verweij J, et al. STI571, an active drug in metastatic gastrointestinal stromal tumors (GIST) an EORTC phase I study [abstract]. Proc Am Soc Clin Oncol 2001;20.1.
109. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347: 472-480. (Pubitemid 34879334)
110. Blanke CD, Rankin C, Demetri GD, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008;26:626-632. (Pubitemid 351264358)
111. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004;364:1127-1134. (Pubitemid 39296599)
112. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol 2010;28:1247-1253.
113. Von M. M, Heinrich MC, Joensuu H, et al. Follow-up results after 9 years (yrs) of the ongoing, phase II B2222 trial of imatinib mesylate (IM) in patients (pts) with metastatic or unresectable KIT\+ gastrointestinal stromal tumors (GIST). J Clin Oncol 2011;29:609s(Suppl) abstr 10016.
114. DeMatteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009;373:1097-1104.
115. Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 2012;307:1265-1272.
116. Cassier PA, Ducimetière F, Lurkin A, et al. A prospective epidemiological study of new incident GISTs during two consecutive years in Rhône Alpes region: incidence and molecular distribution of GIST in a European region. Br J Cancer 2010;103: 165-170.
117. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005;29:52-68. (Pubitemid 40023952)
118. Miettinen M, Makhlouf H, Sobin LH, et al. Gastrointestinal stromal tumors of the jejunum and ileum:clinicopathologic immunohistochemical and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol 2006;30: 477-489. (Pubitemid 43740149)
119. Miettinen M, Kopczynski J, Makhlouf HR, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol 2003;27:625-641. (Pubitemid 36514473)
120. Agaimy A, Vassos N, Märkl B, et al. Anorectal gastrointestinal stromal tumors: a retrospective multicenter analysis of 15 cases emphasizing their high local recurrence rate and the need for standardized therapeutic approach. Int J Colorectal Dis 2013;28: 1057-1064.
121. Le Cesne A, Ray-Coguard I, Bui BN, et al. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol 2010;11:942-949.
122. Agaram NP, Besmer P, Wong GC, et al. Pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive gastrointestinal stromal tumors. Clin Cancer Res 2007;13:170-181. (Pubitemid 46121866)
123. Antonescu CR, Romeo S, Zhang L, et al. Dedifferentiation in gastrointestinal stromal tumor to an anaplastic KIT-negative phenotype: a diagnostic pitfall: morphologic and molecular characterization of 8 cases occurring either de novo or after imatinib therapy. Am J Surg Pathol 2013;37:385-392.
124. Heinrich MC, Owzar K, Corless CL, et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol 2008;26:5360-5367.
125. Debiec-Rychter M, Sciot R, Le CA, et al. Kit mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006;42:1093-1103. (Pubitemid 44275331)
126. Heinrich MC, Maki RG, Corless CL, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008;26:5352-5359.
127. Corless CL, Schroeder A, Griffith D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005;23:5357-5364. (Pubitemid 46206989)
128. Weisberg E, Wright RD, Jiang J, et al. Effects of PKC412, nilotinib, and imatinib against GISTassociated PDGFRA mutants with differential imatinib sensitivity. Gastroenterology 2006;131: 1734-1742. (Pubitemid 44958515)
129. Gajiwala KS, Wu JC, Christensen J, et al. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci USA 2009;106:1542-1547.
130. Cassier PA, Fumagalli E, Rutkowski P, et al. Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Clin Cancer Res 2012;18:4458-4464.
131. Agaimy A, Terracciano LM, Dirnhofer S, et al. V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J Clin Pathol 2009;62: 613-616.
132. Agaram NP, Wong GC, Guo T, et al. Novel V600E BRAF mutations in
133. Janeway KA, Albritton KH, Van den Abbeele AD, et al. Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer 2009;52:767-771.
134. Chen LL, Trent JC, Wu EF, et al. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 2004;64:5913-5919. (Pubitemid 39129383)
135. Debiec-Rychter M, van OA, Marynen P. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 2005;128:270-279. (Pubitemid 40431080)
136. Grimpen F, Yip D, McArthur G, et al. Resistance to imatinib, low-grade FDG-avidity on PET, and acquired KIT exon 17 mutation in gastrointestinal stromal tumour. Lancet Oncol 2005;6:724-727. (Pubitemid 41222764)
137. Heinrich MC, Corless CL, Blanke CD, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 2006;24: 4764-4774. (Pubitemid 46630941)
138. Koyama T, Nimura H, Kobayashi K, et al. Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a novel c-kit mutation after imatinib treatment. Gastric Cancer 2006;9: 235-239. (Pubitemid 44426899)
139. Wakai T, Kanda T, Hirota S, et al. Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation. Br J Cancer 2004;90:2059-2061. (Pubitemid 38869705)
140. Wardelmann E, Thomas N, Merkelbach-Bruse S, et al. Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol 2005;6:249-251. (Pubitemid 40450717)
141. Liegl B, Kepten I, Le C, et al. Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol 2008;216:64-74.
142. 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. Cancer Sci 2008.
143. Lim KH, Huang MJ, Chen LT, et al. Molecular analysis of secondary kinase mutations in imatinib-resistant gastrointestinal stromal tumors. Med Oncol 2008;25:207-213.
144. Demetri GD. Differential properties of current tyrosine kinase inhibitors in gastrointestinal stromal tumors. Semin Oncol 2011;38(Suppl 1):S10-S19.
145. Demetri GD, Van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368:1329-1338. (Pubitemid 44528723)
146. Nishida T, Takahashi T, Nishitani A, et al. Sunitinibresistant gastrointestinal stromal tumors harbor cismutations in the activation loop of the KIT gene. Int J Clin Oncol 2009;14:143-149.
147. Demetri GD, Reichardt P, Kang Y, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. [abstract]. Lancet 2013;381:295-302.
148. Eide CA, Adrian LT, Tyner JW, et al. The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile. Cancer Res 2011;71:3189-3195.
149. Heinrich MC, Wise S, Hood M, et al. In vitro activity of novel KIT/PDGFRA switch pocket kinase inhibitors against mutations associated with drug-resistant GI stromal tumors. J Clin Oncol 2010;28:15s(Suppl) abstr 10007.
150. Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol 2006;23:91-102. (Pubitemid 44692417)