Seminars in Diagnostic Pathology
Volume 23, Issue 2 , Pages 91-102 , May 2006

KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)

  • Jerzy Lasota, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests and correspondence: Jerzy Lasota, MD, Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, 6825 16th Street, N.W., Bldg. 54, Washington, DC 20306-6000.
    • ,
  • Markku Miettinen, MD

References 

  1. Besmer P, Murphy JE, George PC, et al. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature. 1986;320:415–421
  2. Matsui T, Heidaran M, Miki T, et al. Isolation a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989;243:800–804
  3. Roberts WM, Look AT, Ruossel MF, et al. Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes. Cell. 1989;55:655–661
  4. Stenman G, Eriksson A, Claesson-Welsh L. Human PDGFA receptor gene maps to the same region on chromosome 4 as the KIT oncogene. Genes Chromosomes Cancer. 1989;1:155–158
  5. Pawson T. Regulation and targets of receptor tyrosine kinases. Eur J Cancer. 2002;38:S3–S10
  6. Fletcher JA. Role of KIT and platelet-derived growth factor receptors as oncoproteins. Semin Oncol. 2004;31(suppl 6):4–11
  7. Yarden Y, Kuang WJ, Yang Feng T, et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987;6:3341–3351
  8. Chabot B, Stephenson DA, Chapman VM, et al. The protooncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988;335:88–89
  9. Williams DE, Eisenman J, Baird A, et al. Identification of a ligand for the c-kit protooncogene. Cell. 1990;63:167–174
  10. Zsebo KM, Williams DA, Geissler EN, et al. Stem cell factor is encoded at the S1 locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. 1990;63:213–224
  11. Blume-Jensen P, Claesson-Welsh L, Siegbahn A, et al. Activation of the human c-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis. EMBO J. 1991;10:4121–4128
  12. Maeda H, Yamagata A, Nishikawa S, et al. Requirement of c-kit for development of intestinal pacemaker system. Development. 1992;116:369–375
  13. Lev S, Blechman J, Nishikawa S, et al. Interspecies molecular chimeras of kit helps define the binding site of the stem cell factor. Mol Cell Biol. 1993;13:2224–2234
  14. Huizinga JD. Gastrointestinal peristalsis: joint action of enteric nerves, smooth muscle, and interstitial cells of Cajal. Microsc Res Tech. 1999;47:239–247
  15. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–580
  16. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–710
  17. Longley BJ, Reguera MJ, Ma Y. Classes of c-KIT activating mutations: proposed mechanisms of action and implications in disease classification and therapy. Leuk Res. 2001;25:571–576
  18. Heinrich MC, Rubin BP, Longley BJ, et al. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Human Pathol. 2002;33:484–495
  19. London CA, Galli SJ, Yuuki T, et al. Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit. Exp Hematol. 1999;27:689–697
  20. Ma Y, Longley BJ, Wang X, et al. Clustering of activating mutations in c-KIT’s juxtamembrane coding region in canine mast cell neoplasms. J Invest Dermatol. 1999;112:165–170
  21. Nakahara M, Isozaki K, Hirota S, et al. A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors. Gastroenterology. 1998;115:1090–1095
  22. 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
  23. Isozaki K, Terris B, Belghiti J, et al. Germline-activating mutation in the kinase domain on KIT gene in familial gastrointestinal stromal tumors. Am J Pathol. 2001;157:1581–1585
  24. 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
  25. 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
  26. 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
  27. 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
  28. Robson ME, Glogowski E, Sommer G, et al. Pleomorphic characteristics of a germ-line KIT mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and dysphagia. Clin Cancer Res. 2004;10:1250–1254
  29. Carballo M, Roig I, Aquilar F, et al. Novel c-KIT germline mutation in a family with gastrointestinal stromal tumors and coutaneous hyperpigmantation. Am J Med Genet A. 2005;132:361–364
  30. Li FP, Fletcher JA, Heinrich MC, et al. Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol. 2005;23:2735–2743
  31. Tarn C, Merkel E, Canutescu AA, et al. Analysis of KIT mutations in sporadic and familial gastrointestinal stromal tumors: therapeutic implications through protein modeling. Clin Cancer Res. 2005;11:3668–3677
  32. O’Riain C, Corless CL, Heinrich MC, et al. Gastrointestinal stromal tumors: insights fro a new familial GIST kindred with unusual genetic and pathologic features. Am J Surg Pathol. 2005;29:1680–1683
  33. Lasota J, Miettinen M. A new familial GIST identified. Am J Surg Pathol. 2006;30:1342
  34. 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
  35. 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
  36. 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
  37. Ogasawara N, Tsukamoto T, Inada K, et al. Frequent c-KIT gene mutations not only in gastrointestinal stromal tumors but also in interstitial cells of Cajal in surrounding normal tissue. Cancer Letter. 2005;230:199–210
  38. Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumors. Pathol Int. 2006;56:1–9
  39. 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
  40. 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 two hundred cases). Am J Pathol. 2000;157:1091–1095
  41. Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 2001;61:8118–8121
  42. Lasota J, Dansonka-Mieszkowska A, Sobin LH, et al. A great majority of GISTs with PDGFRA mutations represents gastric tumors of low or no malignant potential. Lab Invest. 2004;84:874–883
  43. 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
  44. Lasota J, Stachura J, Miettinen M. GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology. Lab Invest. 2006;86:94–100
  45. Beghini A, Ripamonti CB, Cairoli R, et al. KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. Haematologica. 2004;89:920–925
  46. Wang YY, Zhou GB, Yin T, et al. AML1-ETO and c-kit mutation/overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec. Proc Natl Acad Sci USA. 2005;102:1104–1109
  47. Longley BJ, Tyrrell L, Lu S-Z, et al. Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishement of clonality in a human mast cell neoplasm. Nat Genet. 1996;12:312–314
  48. Longley BJ, Metcalfe DD, Tharp M. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci USA. 1999;96:1609–1614
  49. Hongyo T, Li T, Syaifudin M, et al. Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan. Cancer Res. 2000;60:2345–2347
  50. Tian Q, Frierson HF, Krystal GW, et al. Activating c-kit gene mutations in human germ cell tumors. Am J Pathol. 1999;154:1643–1647
  51. Przygodzki RM, Hubbs AE, Zhao F-Q, et al. Primary mediastinal seminomas: evidence of single and multiple KIT mutations. Lab Invest. 2002;82:1369–1375
  52. Kemmer K, Corless CL, Fletcher JA, et al. KIT mutations are common in testicular seminomas. Am J Pathol. 2004;164:305–313
  53. Hartmann K, Wardelmann E, Ma Y, et al. Novel germline mutation of KIT associated with familial gastrointestinal stromal tumors and mastocytosis. Gastroenterology. 2005;129:1042–1046
  54. 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
  55. 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
  56. Sakurai S, Oguni S, Hironaka M, et al. Mutations in c-kit gene exons 9 and 13 in gastrointestinal stromal tumors among Japanese. Jpn J Cancer Res. 2001;92:494–498
  57. Andersson J, Sjogren H, Meis-Kindblom JM, et al. The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. Am J Pathol. 2002;160:15–22
  58. Lee JH, Zhang X, Jung WY, et al. DNA ploidy and c-KIT mutation in gastrointestinal stromal tumors. World J Gastroenterol. 2004;10:3475–3479
  59. Emile JF, Theou N, Tabone S, et al. Clinicopathologic, phenotypic, and genotypic characteristics of gastrointestinal mesenchymal tumors. Clin Gastroenterol Hepatol. 2004;2:597–605
  60. Sakurai S, Fukasawa T, Chong JM, et al. C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal). Jpn J Cancer Res. 1999;90:1321–1328
  61. Martin J, Poveda J, 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
  62. Williams C, Ponten F, Moberg C, et al. A high frequency of sequence alterations is due to formalin fixation of archival specimens. Am J Pathol. 1999;155:1467–1471
  63. Vu HA, Xinh PT, Kikushima M, et al. A recurrent duodenal gastrointestinal stromal tumor with a frameshift mutation resulting in a stop codon in KIT exon 13. Genes Chromosomes Cancer. 2005;42:179–183
  64. 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
  65. 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 Cancer. 2006;28:1361–1367
  66. Debiec-Rychter M, Cools J, Dumez H, et al. Mechanisms of resistence to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroentereology. 2005;128:270–279
  67. Kikuchi , Yamashita K, Kawabata T, et al. Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: sequential analyses. Cancer Sci. 2006;97:127–132
  68. Crosier PS, Ricciardi ST, Hall LR, et al. Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. Blood. 1993;82:1151–1158
  69. Zhu WM, Dong WF, Minden M. Alternative splicing creates two forms of the human kit protein. Leuk Lymphoma. 1994;12:441–447
  70. Lasota J, Kopczynski J, Majidi M, et al. Apparent KIT Ser715 deletion in GISTs mRNA is not detectable in genomic DNA and represents a previously known splice variant of KIT transcript. Am J Pathol. 2002;161:739–741
  71. Lasota J, Kopczynski J, Sarlomo-Rikala M, et al. KIT 1530ins6 mutation defines a subset of predominantly malignant gastrointestinal stromal tumors of intestinal origin. Human Pathol. 2003;34:1306–1312
  72. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations in imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–4349
  73. Hostein I, Longy M, Gastaldello B, et al. Detection of a new mutation in KIT exon 9 in a gastrointestinal stromal tumor. Int J Cancer. 2006;118:2089–2091
  74. Antonescu CR, Sommer G, Sarran L, et al. Association of KIT exon 9 mutation with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res. 2003;9:3329–3337
  75. Hirota S, Nishida T, Isozaki K, et al. Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours. J Pathol. 2001;193:505–510
  76. Wardelmann E, Hrychyk A, Markelbach-Bruse S, et al. Association of platelet-derived growth factor receptor α mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors. J Mol Diagn. 2004;6:197–204
  77. Subramanian S, West R, Corless CL, et al. Gastrointestinal stromal tumors (GISTs) wit KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene. 2004;23:7780–7790
  78. 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
  79. Koay MHE, Goh Y-W, Iacopetta B, et al. Gastrointestinal stromal tuomours (GISTs): a clinicopathological and molecular study of 66 cases. Pathology. 2005;37:22–31
  80. Tornillo L, Duchini G, Carafa V, et al. Patterns of gene amplification in gastrointestinal stromal tumors (GIST). Lab Invest. 2005;85:921–931
  81. 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
  82. Yamamoto H, Oda Y, Kawaguchi K, et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol. 2004;28:479–488
  83. Kim TW, Lee H, Kang Y-K, et al. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res. 2004;10:3076–3081
  84. Kang HJ, Nam SW, Kim H, et al. Correlation of KIT and platelet-derived growth factor receptor α mutations with gene activation and expression profiles in gastrointestinal stromal tumors. Oncogene. 2005;24:1066–1074
  85. Wardelmann E, Neidt I, Bierhoff E, et al. c-kit mutations in gastrointestinal stromal tumors occur preferentially in the spindle rather than in the epithelioid cell variant. Mod Pathol. 2002;15:125–136
  86. Corless CL, McGreevey L, Town A, et al. KIT gene deletion at the intron 10-exon 11boundry in GI stromal tumors. J Mol Diag. 2004;6:366–370
  87. Chen LL, Sabripour M, Wu EF, et al. A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors. Oncogene. 2005;24:4271–4280
  88. Bumming P, Andersson J, Meis-Kindblom JM, et al. Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Cancer Res UK. 2003;89:460–464
  89. Chen LL, Trent JC, Wu EF, et al. A missense mutation in KIT domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res. 2004;64:5913–5919
  90. 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
  91. Li QS, O’Leary TJ, Sobin LH, et al. Analysis of KIT mutation and protein expression in fine needle aspirates of gastrointestinal stromal/smooth muscle tumors. Acta Cytol. 2000;44:981–986
  92. Morey AL, Wanigesekera D, Hawkins NJ, et al. c-kit mutations in gastrointestinal stromal tumours. Pathology. 2002;34:315–319
  93. Theou N, Gil S, Devocelle A, et al. Multidrug resistance proteins in gastrointestinal stromal tumors: site-dependent expression and initial response to imatinib. Clin Cancer Res. 2005;11:7593–7598
  94. Frost DF, Lasota J, Miettinen M. Gastrointestinal stromal tumors and leiomyomas in the dog-a clinicopathologic, immunohistochemical molecular genetic study of 50 cases. Vet Pathol. 2003;61:42–54
  95. Went P, Dirnhofer S, Bundi M, et al. Prevalence of KIT expression in human tumors. J Clin Oncol. 2004;22:4514–4522
  96. Willmore-Payne C, Holden JA, Hirschowitz S, et al. BRAF and c-kit gene copy number in mutation positive malignant melanoma. Hum Pathol. 2006;37:520–527
  97. Choi YR, Kim H, Kang HJ, et al. Overexpression of high mobility group box 1 in gastrointestinal stromal tumors wit KIT mutation. Cancer Res. 2003;63:2188–2193
  98. Moskaluk CA, Tian Q, Marshall CR, et al. Mutations of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors. Oncogene. 1999;18:1897–1902
  99. Feng F, Liu XH, Xie Q, et al. Expression and mutation of c-kit gene in gastrointestinal stromal tumors. Worl J Gastroenterol. 2003;9:2548–2551
  100. Hou YY, Tan YS, Sun MH, et al. C-kit gene mutation in gastrointestinal stromal tumors. Worl J Gastroenterol. 2004;10:1310–1314
  101. Lasota J, Dansonka-Mieszkowska A, Stachura T, et al. Gastrointestinal stromal tumors with internal tandem duplications in 3′ end of KIT juxtamembrane domain occur predominantly in stomach and generally seem to have a favorable course. Mod Pathol. 2003;16:1257–1264
  102. Corbacioglu S, Kilic M, Westhoff MA, et al. Newly identified c-kit receptor tyrosine kinase ITD in childhood AML induces ligand independent growth and is responsive to a synergistic effect of imatinib and rapamycin. Blood. 2006;E-pub 1-26, July 13
  103. Yokota S, Kiyoi H, Nakao M, et al. Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies: a study on a large series of patients and cell lines. Leukemia. 1997;11:1605–1609
  104. Zwaan CM, Meshinchi S, Radich JP, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellulare drug resistance. Blood. 2003;102:2387–2394
  105. Miettinen M, Monihan JM, Sarlomo-Rikala M, et al. Gastrointestinal stromal tumors/smooth muscle tumors/GISTs in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol. 1999;23:1109–1118
  106. Miettinen M, Sarlomo-Rikala M, Sobin LH, et al. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol. 2000;24:211–222
  107. Miettinen M, Sarlomo-Rikala M, Sobin LH, et al. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical and molecular genetic study of 44 cases. Am J Surg Pathol. 2000;24:1339–1352
  108. Miettinen M, Furlong M, Sarlomo-Rikala M, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus (A clinicopathologic, immunohistochemical and molecular genetic study of 144 cases). Am J Surg Pathol. 2001;25:1121–1133
  109. Miettinen M, Sobin LH. Gastrointestinal stromal tumors in the appendix: a clinicopathologic and immunohistochemical study of four cases. Am J Surg Pathol. 2001;25:1433–1437
  110. Miettinen M, Kopczynski J, Maklouf 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
  111. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors (GISTs) of the stomach: a clinicopathologic, immunohistochemical and molecular genetic study of 1756 cases with long-term follow-up. Am J Surg Pathol. 2005;29:52–68
  112. Miettinen M, Makhlouf H, Sobin LH, et al. Gastrointestinal stromal tumors (GISTs) of the jejunum and ileum: a clinicopathologic, immunohistochemical and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol. 2006;30:477–489
  113. Haller F, Gunawan B, von Heydebreck A, et al. Prognostic role of E2F1 and members of the CDKN2A network in gastrointestinal stromal tumors. Clin Cancer Res. 2005;11:6589–6597
  114. He HY, Xiang YN, Zhong HH, et al. c-kit and PDGFRS mutations in 60 cases of gastrointestinal tumors (GISTs). Beijing Da Xue Xue Bao. 2005;37:320–324
  115. Che 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
  116. 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
  117. Hirota S, Ohashi A, Nishida T, et al. Gain-of-function mutations of platelet-derived growth factor receptor α gene in gastrointestinal stromal tumors. Gastroenterology. 2003;125:660–667
  118. 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
  119. 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
  120. Takazawa Y, Sakurai S, Sakuma Y, et al. Gastrointestinal stromal tumors of neurofibromatosis type I (von Recklinghausen’s disease). Am J Surg Pathol. 2005;29:755–763
  121. Yantiss R, Rosenberg AE, Sarran L, et al. Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study. Modern Pathol. 2005;18:475–484
  122. Bumming P, Nilsson B, Sorensen J, et al. Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and pheochromocytoma in patients with Carney triad and neurofibromatosis type 1. Scand J Gastroenterol. 2005;41:626–630
  123. 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
  124. Nemoto H, Tate G, Schirinzi A, et al. Novel NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 and a gastrointestinal stromal tumor. J Gastroenterol. 2006;41:378–382
  125. Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults. Am J Surg Pathol. 2005;29:1–9
  126. 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
  127. O’Sullivan MJ, McCabe A, Gillett P, et al. Multiple gastric stromal tumors in a child without syndromic association lacks common KIT or PDGFRalpha mutations. Pediatr Dev Pathol. 2005;8:685–689
  128. Kuroiwa M, Hiwatari M, Hirato J, et al. Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year-old girl with unique mutation of PDGFRA. J Pediatr Surg. 2005;40:1798–1801
  129. Price VE, Zielenska M, Chilton-MacNeill S, et al. Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs). Pediatr Blood Cancer. 2005;45:20–24
  130. Diment J, Tamborini E, Casali P, et al. Carney triad: case report and molecular analysis of gastric tumor. Hum Pathol. 2005;36:112–116
  131. Perry CG, Young WF, McWhinney SR, et al. Functioning paraganglioma and gastrointestinal stromal tumor of the jejunum in three women: syndrome or coincidence. Am J Surg Pathol. 2006;30:42–49
  132. 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
  133. Kinoshita K, Isozaki K, Hirota S, et al. c-kit gene mutation at exon 17 and 13 is very rare in sporadic gastrointestinal stromal tumors. J Gastroenterol Hepatol. 2003;18:147–151
  134. Pauls K, Merkelbach-Bruse S, Buttner R, et al. PDGFRα and c-kit-mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features. Histopathology. 2005;46:166–175
  135. van Oosterom AT, Judson I, Verweij J, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001;358:1421–1423
  136. 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
  137. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24:25–35
  138. Prenen H, Cools J, Mentens N, et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res. 2006;12:2622–2627
  139. Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organization for Research and Treatment of Cancer-Italien Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol. 2005;23:5795–5804
  140. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. 2004;22:3813–3825
  141. Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors. Eur J Cancer. 2006;42:1093–1103
  142. Chen LL, Sabripour M, Andtbacka RHI, et al. Imatinib resistance in gastrointestinal stromla tumors. Curr Oncol Rep. 2005;7:293–299
  143. Tamborini E, Bonadiman L, Greco A, et al. A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology. 2004;127:294–299
  144. Antonescu CR, Besmer P, Guo T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumors occurs through secondary gene mutation. Clin Cancer Res. 2005;11:4182–4190
  145. McLean SR, Gana-Weisz M, Hartzoulakis B, et al. Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala. Mol Cancer Ther. 2005;4:2008–2015
  146. 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
  147. Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006;12:1743–1749

 The opinions and assertions contained herein are the expressed views of the authors and are not to be construed as official or reflecting the views of the Departments of the Army or Defense.

PII: S0740-2570(06)00142-0

doi: 10.1053/j.semdp.2006.08.006

Seminars in Diagnostic Pathology
Volume 23, Issue 2 , Pages 91-102 , May 2006

Article Tools

* Image Usage & Resolution