The genetic landscape of gastrointestinal stromal tumor lacking KIT and PDGFRA mutations

Endocrine

Volumn 47, Issue 2, 2014, Pages 401-408

  Boikos, Sosipatros A ^a   Stratakis, Constantine A ^b  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

BRAF; Chondroma; NF1; Paraganglioma; SDH deficient GIST

Indexed keywords

B RAF KINASE; NEUROFIBROMIN; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; SUCCINATE DEHYDROGENASE; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; STEM CELL FACTOR RECEPTOR;

BRAF MUTATION; CANCER CLASSIFICATION; CARNEY COMPLEX; CARNEY STRATAKIS SYNDROME; COMPARATIVE GENOMIC HYBRIDIZATION; ENZYME DEFICIENCY; ENZYME SUBUNIT; GASTROINTESTINAL STROMAL TUMOR; GENE; GENE MUTATION; GENETIC DISORDER; GENETIC HETEROGENEITY; HUMAN; KIT GENE; NF1 GENE; PARAGANGLIOMA; PATHOGENESIS; PDGFRA GENE; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; SUCCINATE DEHYDROGENASE SUBUNIT DEFICIENT GASTROINTESTINAL STROMAL TUMOR; WILD TYPE; GASTROINTESTINAL TUMOR; GENETICS; MUTATION; PATHOLOGY;

GASTROINTESTINAL NEOPLASMS; GASTROINTESTINAL STROMAL TUMORS; HUMANS; MUTATION; PHENOTYPE; PROTO-ONCOGENE PROTEINS C-KIT; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA;

EID: 84911002207     PISSN: 1355008X     EISSN: 15590100     Source Type: Journal    
DOI: 10.1007/s12020-014-0346-3     Document Type: Review

References (69)

1. C.L. Corless, J.A. Fletcher, M.C. Heinrich, Biology of gastrointestinal stromal tumors. J. Clin. Oncol. 22, 3813–3825 (2004)
2. E.A. Perez, A.S. Livingstone, D. Franceschi, C. Rocha-Lima, D.J. Lee, N. Hodgson, M. Jorda, L.G. Koniaris, Current incidence and outcomes of gastrointestinal mesenchymal tumors including gastrointestinal stromal tumors. J. Am. Coll. Surg. 202, 623–629 (2006)
3. B. Nilsson, P. Bümming, J.M. Meis-Kindblom, A. Odén, A. Dortok, B. Gustavsson, K. Sablinska, L.-G. Kindblom, Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 103, 821–829 (2005)
4. G. Tryggvason, H.G. Gíslason, M.K. Magnússon, J.G. Jónasson, Gastrointestinal stromal tumors in Iceland, 1990–2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int. J. Cancer 117, 289–293 (2005)
5. S. Hirota, K. Isozaki, Y. Moriyama, K. Hashimoto, T. Nishida, S. Ishiguro, K. Kawano, M. Hanada, A. Kurata, M. Takeda, G. Muhammad Tunio, Y. Matsuzawa, Y. Kanakura, Y. Shinomura, Y. Kitamura, Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279, 577–580 (1998)
6. M.C. Heinrich, C.L. Corless, A. Duensing, L. McGreevey, C.-J. Chen, N. Joseph, S. Singer, D.J. Griffith, A. Haley, A. Town, G.D. Demetri, C.D.M. Fletcher, J.A. Fletcher, PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299, 708–710 (2003)
7. P.M. Forde, R.L. Cochran, S.A. Boikos, D.J. Zabransky, J.A. Beaver, C.F. Meyer, K.A. Thornton, E.A. Montgomery, A.O. Lidor, R.C. Donehower, B.H. Park, Familial GI stromal tumor with loss of heterozygosity and amplification of mutant KIT. J. Clin. Oncol. (2014). doi:10.1200/JCO.2013.51.6633
8. B. Pasini, L. Matyakhina, T. Bei, M. Muchow, S. Boikos, B. Ferrando, J.A. Carney, C.A. Stratakis, Multiple gastrointestinal stromal and other tumors caused by platelet-derived growth factor receptor alpha gene mutations: a case associated with a germline V561D defect. J. Clin. Endocrinol. Metab. 92, 3728–3732 (2007)
9. A. Chompret, C. Kannengiesser, M. Barrois, P. Terrier, P. Dahan, T. Tursz, G.M. Lenoir, B. Bressac-De Paillerets, PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology 126, 318–321 (2004)
10. T. Nishida, S. Hirota, M. Taniguchi, K. Hashimoto, K. Isozaki, H. Nakamura, Y. Kanakura, T. Tanaka, A. Takabayashi, H. Matsuda, Y. Kitamura, Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat. Genet. 19, 323–324 (1998)
11. M.A. Postow, M.E. Robson, Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications. Clin. Sarcoma Res. 2, 16 (2012)
12. E.P. Kleinbaum, A.J.F. Lazar, E. Tamborini, J.C. Mcauliffe, P.B. Sylvestre, T.D. Sunnenberg, L. Strong, L.L. Chen, H. Choi, R.S. Benjamin, W. Zhang, J.C. Trent, Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. Int. J. Cancer 122, 711–718 (2008)
13. J.S. Gold, S.M. van der Zwan, M. Gönen, R.G. Maki, S. Singer, M.F. Brennan, C.R. Antonescu, R.P. De Matteo, Outcome of metastatic GIST in the era before tyrosine kinase inhibitors. Ann. Surg. Oncol. 14, 134–142 (2007)
14. G.D. Demetri, M. von Mehren, C.D. Blanke, A.D. Van den Abbeele, B. Eisenberg, P.J. Roberts, M.C. Heinrich, D.A. Tuveson, S. Singer, M. Janicek, J.A. Fletcher, S.G. Silverman, S.L. Silberman, R. Capdeville, B. Kiese, B. Peng, S. Dimitrijevic, B.J. Druker, C. Corless, C.D.M. Fletcher, H. Joensuu, Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347, 472–480 (2002)
15. G.D. Demetri, A.T. van Oosterom, C.R. Garrett, M.E. Blackstein, M.H. Shah, J. Verweij, G. McArthur, I.R. Judson, M.C. Heinrich, J.A. Morgan, J. Desai, C.D. Fletcher, S. George, C.L. Bello, X. Huang, C.M. Baum, P.G. Casali, Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368, 1329–1338 (2006)
16. G.D. Demetri, P. Reichardt, Y.-K. Kang, J.-Y. Blay, P. Rutkowski, H. Gelderblom, P. Hohenberger, M. Leahy, M. von Mehren, H. Joensuu, G. Badalamenti, M. Blackstein, A. Le Cesne, P. Schöffski, R.G. Maki, S. Bauer, B.B. Nguyen, J. Xu, T. Nishida, J. Chung, C. Kappeler, I. Kuss, D. Laurent, P.G. Casali, 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. Lancet 381, 295–302 (2013)
17. K.A. Janeway, K.H. Albritton, A.D. Van Den Abbeele, G.Z. D’Amato, P. Pedrazzoli, S. Siena, J. Picus, J.E. Butrynski, M. Schlemmer, M.C. Heinrich, G.D. Demetri, Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr. Blood Cancer 52, 767–771 (2009)
18. M.C. Heinrich, K. Owzar, C.L. Corless, D. Hollis, E.C. Borden, C.D.M. Fletcher, C.W. Ryan, M. von Mehren, C.D. Blanke, C. Rankin, R.S. Benjamin, V.H. Bramwell, G.D. Demetri, M.M. Bertagnolli, J.A. Fletcher, 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. 26, 5360–5367 (2008)
19. J.A. Carney, S.G. Sheps, V.L. Go, H. Gordon, The triad of gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma. N. Engl. J. Med. 296, 1517–1518 (1977)
20. J.A. Carney, C.A. Stratakis, Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am. J. Med. Genet. 108, 132–139 (2002)
21. S.R. McWhinney, B. Pasini, C.A. Stratakis, Familial gastrointestinal stromal tumors and germ-line mutations. N. Engl. J. Med. 357, 1054–1056 (2007)
22. K.A. Janeway, S.Y. Kim, M. Lodish, V. Nosé, P. Rustin, J. Gaal, P.L.M. Dahia, B. Liegl, E.R. Ball, M. Raygada, A.H. Lai, L. Kelly, J.L. Hornick, M. O’Sullivan, R.R. de Krijger, W.N.M. Dinjens, G.D. Demetri, C.R. Antonescu, J.A. Fletcher, L. Helman, C.A. Stratakis, Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc. Natl. Acad. Sci. USA 108, 314–318 (2011)
23. M.A. Selak, S.M. Armour, E.D. MacKenzie, H. Boulahbel, D.G. Watson, K.D. Mansfield, Y. Pan, M.C. Simon, C.B. Thompson, E. Gottlieb, Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7, 77–85 (2005)
24. J.K. Killian, S.Y. Kim, M. Miettinen, C. Smith, M. Merino, M. Tsokos, M. Quezado, W.I. Smith, M.S. Jahromi, P. Xekouki, E. Szarek, R.L. Walker, J. Lasota, M. Raffeld, B. Klotzle, Z. Wang, L. Jones, Y. Zhu, Y. Wang, J.J. Waterfall, M.J. O’Sullivan, M. Bibikova, K. Pacak, C. Stratakis, K.A. Janeway, J.D. Schiffman, J.-B. Fan, L. Helman, P.S. Meltzer, Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov. 3, 648–657 (2013)
25. M. Tahiliani, K.P. Koh, Y. Shen, W.A. Pastor, H. Bandukwala, Y. Brudno, S. Agarwal, L.M. Iyer, D.R. Liu, L. Aravind, A. Rao, Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009)
26. M. Xiao, H. Yang, W. Xu, S. Ma, H. Lin, H. Zhu, L. Liu, Y. Liu, C. Yang, Y. Xu, S. Zhao, D. Ye, Y. Xiong, K.-L. Guan, Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326–1338 (2012)
27. W.G. Kaelin, S.L. McKnight, Influence of metabolism on epigenetics and disease. Cell 153, 56–69 (2013)
28. M. Yang, P.J. Pollard, Succinate: a new epigenetic hacker. Cancer Cell 23, 709–711 (2013)
29. A. Agaimy, L.M. Terracciano, S. Dirnhofer, L. Tornillo, A. Foerster, A. Hartmann, M.P. Bihl, V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J. Clin. Pathol. 62, 613–616 (2009)
30. H. Yamamoto, T. Tobo, M. Nakamori, M. Imamura, A. Kojima, Y. Oda, N. Nakamura, T. Takahira, T. Yao, M. Tsuneyoshi, Neurofibromatosis type 1-related gastrointestinal stromal tumors: a special reference to loss of heterozygosity at 14q and 22q. J. Cancer Res. Clin. Oncol. 135, 791–798 (2009)
31. M.P. Grace, G. Batist, W.R. Grace, J.F. Gillooley, Aorticopulmonary paraganglioma and gastric leiomyoblastoma in a young woman. Am. J. Med. 70, 1288–1292 (1981)
32. J.A. Carney, Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney Triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin. Proc. 74, 543–552 (1999)
33. L. Matyakhina, T.A. Bei, S.R. McWhinney, B. Pasini, S. Cameron, B. Gunawan, S.G. Stergiopoulos, S. Boikos, M. Muchow, A. Dutra, E. Pak, E. Campo, M.C. Cid, F. Gomez, R.C. Gaillard, G. Assie, L. Füzesi, B.E. Baysal, C. Eng, J.A. Carney, C.A. Stratakis, Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors. J. Clin. Endocrinol. Metab. 92, 2938–2943 (2007)
34. J. Gaal, C.A. Stratakis, J.A. Carney, E.R. Ball, E. Korpershoek, M.B. Lodish, I. Levy, P. Xekouki, F.H. van Nederveen, M.A. den Bakker, M. O’Sullivan, W.N.M. Dinjens, R.R. de Krijger, SDHB immunohistochemistry: a useful tool in the diagnosis of Carney–Stratakis and Carney triad gastrointestinal stromal tumors. Mod. Pathol. 24, 147–151 (2011)
35. L. Zhang, T.C. Smyrk, W.F. Young, C.A. Stratakis, J.A. Carney, Gastric stromal tumors in Carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: findings in 104 cases. Am. J. Surg. Pathol. 34, 53–64 (2010)
36. B. Pasini, S.R. McWhinney, T. Bei, L. Matyakhina, S. Stergiopoulos, M. Muchow, S.A. Boikos, B. Ferrando, K. Pacak, G. Assie, E. Baudin, A. Chompret, J.W. Ellison, J.-J. Briere, P. Rustin, A.-P. Gimenez-Roqueplo, C. Eng, J.A. Carney, C.A. Stratakis, Clinical and molecular genetics of patients with the Carney–Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur. J. Hum. Genet. 16, 79–88 (2008)
37. L. Oudijk, J. Gaal, E. Korpershoek, F.H. van Nederveen, L. Kelly, G. Schiavon, J. Verweij, R.H.J. Mathijssen, M.A. den Bakker, R.A. Oldenburg, R.L.E. van Loon, M.J. O’Sullivan, R.R. de Krijger, W.N.M. Dinjens, SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors. Mod. Pathol. 26, 456–463 (2013)
38. A.J. Wagner, S.P. Remillard, Y.-X. Zhang, L.A. Doyle, S. George, J.L. Hornick, Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. Mod. Pathol. 26, 289–294 (2013)
39. M. Miettinen, J.K. Killian, Z.-F. Wang, J. Lasota, C. Lau, L. Jones, R. Walker, M. Pineda, Y.J. Zhu, S.Y. Kim, L. Helman, P. Meltzer, Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation. Am. J. Surg. Pathol. 37, 234–240 (2013)
40. O. Maertens, H. Prenen, M. Debiec-Rychter, A. Wozniak, R. Sciot, P. Pauwels, I. De Wever, J.R. Vermeesch, T. de Raedt, A. De Paepe, F. Speleman, A. van Oosterom, L. Messiaen, E. Legius, Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum. Mol. Genet. 15, 1015–1023 (2006)
41. M. Miettinen, J. Lasota, Gastrointestinal stromal tumors. Gastroenterol. Clin. North Am. 42, 399–415 (2013)
42. J.H. Wang, J. Lasota, M. Miettinen, Succinate dehydrogenase subunit B (SDHB) is expressed in neurofibromatosis 1-associated gastrointestinal stromal tumors (GISTs): implications for the SDHB expression based classification of GISTs. J. Cancer 2, 90–93 (2011)
43. J. Lasota, Z. Wang, S.Y. Kim, L. Helman, M. Miettinen, Expression of the receptor for type i insulin-like growth factor (IGF1R) in gastrointestinal stromal tumors: an immunohistochemical study of 1078 cases with diagnostic and therapeutic implications. Am. J. Surg. Pathol. 37, 114–119 (2013)
44. J.-L. Lee, J.Y. Kim, M.-H. Ryu, H.J. Kang, H.M. Chang, T.-W. Kim, H. Lee, J.H. Park, H.C. Kim, J.S. Kim, Y.-K. Kang, Response to imatinib in KIT- and PDGFRA-wild type gastrointestinal stromal associated with neurofibromatosis type 1. Dig. Dis. Sci. 51, 1043–1046 (2006)
45. C. Mussi, H.-U. Schildhaus, A. Gronchi, E. Wardelmann, P. Hohenberger, Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1. Clin. Cancer Res. 14, 4550–4555 (2008)
46. N.P. Agaram, G.C. Wong, T. Guo, R.G. Maki, S. Singer, R.P. Dematteo, P. Besmer, C.R. Antonescu, Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosom. Cancer 47, 853–859 (2008)
47. C. Miranda, M. Nucifora, F. Molinari, E. Conca, M.C. Anania, A. Bordoni, P. Saletti, L. Mazzucchelli, S. Pilotti, M.A. Pierotti, E. Tamborini, A. Greco, M. Frattini, KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors. Clin. Cancer Res. 18, 1769–1776 (2012)
48. G.S. Falchook, J.C. Trent, M.C. Heinrich, C. Beadling, J. Patterson, C.C. Bastida, S.C. Blackman, R. Kurzrock, BRAF mutant gastrointestinal stromal tumor: first report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance. Oncotarget 4, 310–315 (2013)
49. L.G. Kindblom, H.E. Remotti, F. Aldenborg, J.M. Meis-Kindblom, Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am. J. Pathol. 152, 1259–1269 (1998)
50. M. Miettinen, Z.-F. Wang, M. Sarlomo-Rikala, C. Osuch, P. Rutkowski, J. Lasota, Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am. J. Surg. Pathol. 35, 1712–1721 (2011)
51. F.H. Van Nederveen, J. Gaal, J. Favier, E. Korpershoek, R.A. Oldenburg, E.M.C.A. de Bruyn, H.F.B.M. Sleddens, P. Derkx, J. Rivière, H. Dannenberg, B.-J. Petri, P. Komminoth, K. Pacak, W.C.J. Hop, P.J. Pollard, M. Mannelli, J.-P. Bayley, A. Perren, S. Niemann, A.A. Verhofstad, A.P. de Bruïne, E.R. Maher, F. Tissier, T. Méatchi, C. Badoual, J. Bertherat, L. Amar, D. Alataki, E. Van Marck, F. Ferrau, J. François, W.W. de Herder, M.P.F.M.V. Peeters, A. van Linge, J.W.M. Lenders, A.-P. Gimenez-Roqueplo, R.R. de Krijger, W.N.M. Dinjens, An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol. 10, 764–771 (2009)
52. T.A. Rege, A.J. Wagner, C.L. Corless, M.C. Heinrich, J.L. Hornick, “Pediatric-type” gastrointestinal stromal tumors in adults: distinctive histology predicts genotype and clinical behavior. Am. J. Surg. Pathol. 35, 495–504 (2011)
53. L.A. Doyle, D. Nelson, M.C. Heinrich, C.L. Corless, J.L. Hornick, Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: a comprehensive genotype-phenotype correlation study. Histopathology 61, 801–809 (2012)
54. H.-X. Hao, O. Khalimonchuk, M. Schraders, N. Dephoure, J.-P. Bayley, H. Kunst, P. Devilee, C.W.R.J. Cremers, J.D. Schiffman, B.G. Bentz, S.P. Gygi, D.R. Winge, H. Kremer, J. Rutter, SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 325, 1139–1142 (2009)
55. E. Letouzé, C. Martinelli, C. Loriot, N. Burnichon, N. Abermil, C. Ottolenghi, M. Janin, M. Menara, A.T. Nguyen, P. Benit, A. Buffet, C. Marcaillou, J. Bertherat, L. Amar, P. Rustin, A. De Reyniès, A.-P. Gimenez-Roqueplo, J. Favier, SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 23, 739–752 (2013)
56. A.J. Gill, N.S. Pachter, A. Chou, B. Young, A. Clarkson, K.M. Tucker, I.M. Winship, P. Earls, D.E. Benn, B.G. Robinson, S. Fleming, R.J. Clifton-Bligh, Renal tumors associated with germline SDHB mutation show distinctive morphology. Am. J. Surg. Pathol. 35, 1578–1585 (2011)
57. P. Xekouki, C.A. Stratakis, Succinate dehydrogenase (SDHx) mutations in pituitary tumors: could this be a new role for mitochondrial complex II and/or Krebs cycle defects? Endocr. Relat. Cancer 19, C33–C40 (2012)
58. P. Xekouki, K. Pacak, M. Almeida, C.A. Wassif, P. Rustin, M. Nesterova, M. de la Luz Sierra, J. Matro, E. Ball, M. Azevedo, A. Horvath, C. Lyssikatos, M. Quezado, N. Patronas, B. Ferrando, B. Pasini, A. Lytras, G. Tolis, C.A. Stratakis, Succinate dehydrogenase (SDH) D subunit (SDHD) inactivation in a growth-hormone-producing pituitary tumor: a new association for SDH? J. Clin. Endocrinol. Metab. 97, E357–E366 (2012)
59. L. Kelly, K. Bryan, S.Y. Kim, K.A. Janeway, J.K. Killian, H.-U. Schildhaus, M. Miettinen, L. Helman, P.S. Meltzer, M. van de Rijn, M. Debiec-Rychter, M. O’Sullivan, Post-transcriptional dysregulation by miRNAs is implicated in the pathogenesis of gastrointestinal stromal tumor [GIST]. PLoS ONE 8, e64102 (2013)
60. W.K. Kim, M. Park, Y.-K. Kim, Y.K. Tae, H.-K. Yang, J.M. Lee, H. Kim, MicroRNA-494 downregulates KIT and inhibits gastrointestinal stromal tumor cell proliferation. Clin. Cancer Res. 17, 7584–7594 (2011)
61. S. George, Q. Wang, M.C. Heinrich, C.L. Corless, M. Zhu, J.E. Butrynski, J.A. Morgan, A.J. Wagner, E. Choy, W.D. Tap, J.T. Yap, A.D. Van den Abbeele, J.B. Manola, S.M. Solomon, J.A. Fletcher, M. von Mehren, G.D. Demetri, Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J. Clin. Oncol. 30, 2401–2407 (2012)
62. K.N. Ganjoo, V.M. Villalobos, A. Kamaya, G.A. Fisher, J.E. Butrynski, J.A. Morgan, A.J. Wagner, D. D’Adamo, A. McMillan, G.D. Demetri, S. George, A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib. Ann. Oncol. 25, 236–240 (2014)
63. K.A. Janeway, M.-J. Zhu, J. Barretina, A. Perez-Atayde, G.D. Demetri, J.A. Fletcher, Strong expression of IGF1R in pediatric gastrointestinal stromal tumors without IGF1R genomic amplification. Int. J. Cancer 127, 2718–2722 (2010)
64. M.A. Pantaleo, A. Astolfi, M. Di Battista, M.C. Heinrich, P. Paterini, K. Scotlandi, D. Santini, F. Catena, M.C. Manara, M. Nannini, A. Maleddu, M. Saponara, C. Lolli, S. Formica, G. Biasco, Insulin-like growth factor 1 receptor expression in wild-type GISTs: a potential novel therapeutic target. Int. J. Cancer 125, 2991–2994 (2009)
65. A. Chou, J. Chen, A. Clarkson, J.S. Samra, R.J. Clifton-Bligh, T.J. Hugh, A.J. Gill, Succinate dehydrogenase-deficient GISTs are characterized by IGF1R overexpression. Mod. Pathol. 25, 1307–1313 (2012)
66. E. Fox, B.C. Widemann, M.K. Chuk, L. Marcus, A. Aikin, P.O. Whitcomb, M.J. Merino, M. Lodish, E. Dombi, S.M. Steinberg, S.A. Wells, F.M. Balis, Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin. Cancer Res. 19, 4239–4248 (2013)
67. S.A. Wells, J.E. Gosnell, R.F. Gagel, J. Moley, D. Pfister, J.A. Sosa, M. Skinner, A. Krebs, J. Vasselli, M. Schlumberger, Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J. Clin. Oncol. 28, 767–772 (2010)
68. M. Montani, A.M. Schmitt, S. Schmid, T. Locher, P. Saremaslani, P.U. Heitz, P. Komminoth, A. Perren, No mutations but an increased frequency of SDHx polymorphisms in patients with sporadic and familial medullary thyroid carcinoma. Endocr. Relat. Cancer 12, 1011–1016 (2005)
69. K.W. Jasperson, W. Kohlmann, A. Gammon, H. Slack, L. Buchmann, J. Hunt, A.C. Kirchhoff, H. Baskin, A. Shaaban, J.D. Schiffman, Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families. Fam. Cancer 13, 257–265 (2013)