Seminars in Diagnostic Pathology
Volume 23, Issue 2 , Pages 63-69 , May 2006

Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models

  • Cristina R. Antonescu, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests and correspondence: Cristina R. Antonescu, MD, Department of Pathology, Memorial Sloan–Kettering Cancer Center, 1275 York Ave, New York, NY 10021.

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. Huang E, Nocka K, Beier DR, et al. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 5. 1990;63:225–233
  3. Huang EJ, Nocka KH, Buck J, et al. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell. 1992;3:349–362
  4. Mol CD, Dougan DR, Schneider TR, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004;279:31655–31663
  5. Kissel H, Timokhina I, Hardy MP, et al. Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses. EMBO J. 2000;19:1312–1326
  6. Agosti V, Corbacioglu S, Ehlers I, et al. Critical role for Kit-mediated Src kinase but not PI 3-kinase signaling in pro T and pro B cell development. J Exp Med. 2004;199:867–878
  7. Huizinga JD, Thuneberg L, Kluppel M, et al. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373:347–349
  8. Maeda H, Yamagata A, Nishikawa S, et al. Requirement of c-kit for development of intestinal pacemaker system. Development. 1992;116:369–375
  9. Torihashi S, Ward SM, Nishikawa S, et al. c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res. 1995;280:97–111
  10. Ward SM, Burns AJ, Torihashi S, et al. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994;480:91–97
  11. Torihashi S, Nishi K, Tokutomi Y, et al. Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype. Gastroenterology. 1999;117:140–148
  12. 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
  13. Nagata H, Worobec AS, Oh CK, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci USA. 1995;92:10560–10564
  14. Longley BJ, Tyrrell L, Lu SZ, et al. Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm. Nat Genet. 1996;12:312–314
  15. Gari M, Goodeve A, Wilson G, et al. c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol. 1999;105:894–900
  16. Willmore-Payne C, Holden JA, Tripp S, et al. Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol. 2005;36:486–493
  17. 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
  18. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–710
  19. Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 2001;61:8118–8121
  20. Antonescu CR, Sommer G, Sarran L, et al. Association of KIT exon 9 mutations 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. Lasota J, Kopczynski J, Sarlomo-Rikala M, et al. KIT 1530ins6 mutation defines a subset of predominantly malignant gastrointestinal stromal tumors of intestinal origin. Hum Pathol. 2003;34:1306–1312
  26. 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
  27. 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
  28. 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
  29. 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). Am J Pathol. 2000;157:1091–1095
  30. 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
  31. 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
  32. 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
  33. Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol. 2005;29:1373–1381
  34. 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
  35. 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
  36. 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
  37. Debiec-Rychter M, Sciot R, Pauwels P, et al. Molecular cytogenetic definition of three distinct chromosome arm 14q deletion intervals in gastrointestinal stromal tumors. Genes Chromosomes Cancer. 2001;32:26–32
  38. Breiner JA, Meis-Kindblom J, Kindblom LG, et al. Loss of 14q and 22q in gastrointestinal stromal tumors (pacemaker cell tumors). Cancer Genet Cytogenet. 2000;120:111–116
  39. Allander SV, Nupponen NN, Ringner M, et al. Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile. Cancer Res. 2001;61:8624–8628
  40. Segal NH, Pavlidis P, Antonescu CR, et al. Classification and subtype prediction of adult soft tissue sarcoma by functional genomics. Am J Pathol. 2003;163:691–700
  41. Antonescu CR, Viale A, Sarran L, et al. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res. 2004;10:3282–3290
  42. 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
  43. Vanderwinden JM, Rumessen JJ. Interstitial cells of Cajal in human gut and gastrointestinal disease. Microsc Res Tech. 1999;47:344–360
  44. 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
  45. 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
  46. 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
  47. Isozaki K, Terris B, Belghiti J, et al. Germline-activating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors. Am J Pathol. 2000;157:1581–1585
  48. Kitayama H, Tsujimura T, Matsumura I, et al. Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase. Blood. 1996;88:995–1004
  49. 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
  50. 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
  51. 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
  52. 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
  53. 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
  54. 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
  55. Hirota S, Okazaki T, Kitamura Y, et al. Cause of familial and multiple gastrointestinal autonomic nerve tumors with hyperplasia of interstitial cells of Cajal is germline mutation of the c-kit gene. Am J Surg Pathol. 2000;24:326–327
  56. Kim HJ, Lim SJ, Park K, et al. Multiple gastrointestinal stromal tumors with a germline c-kit mutation. Pathol Int. 2005;55:655–659
  57. 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
  58. 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

PII: S0740-2570(06)00139-0

doi: 10.1053/j.semdp.2006.08.003

Seminars in Diagnostic Pathology
Volume 23, Issue 2 , Pages 63-69 , May 2006