Virchows Archiv

, Volume 471, Issue 1, pp 77–90 | Cite as

Clinical and pathological characteristics of gastrointestinal stromal tumor (GIST) metastatic to bone

  • Kemal Kosemehmetoglu
  • Gulsah Kaygusuz
  • Karen Fritchie
  • Ovgu Aydin
  • Ozlem Yapicier
  • Oznur Coskun
  • Ersin Karatayli
  • Senay Boyacigil
  • Gulnur Guler
  • Sergulen Dervisoglu
  • Isinsu Kuzu
Original Article


Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months–20 years). Morphologically, neoplastic cells were spindle in 67%, epithelioid in 13%, and mixed epithelioid and spindle in 20%. CD117, DOG1, and CD34 were positive in 88, 86, and 85% of the cases, respectively. KIT Exon 11 mutations were the most frequent gene alteration (78%), followed by KIT Exon 13 mutations. Of 17 of the cases with available follow-up information, 7 (41%) patients developed bone metastasis under imatinib therapy. Five patients (29%) died of disease within a mean of 17 months. Bone metastases from GIST are usually found in patients with advanced disease and typically present as lytic masses with occasional soft tissue involvement. We could not identify any KIT or PDGFRA alterations predisposing to bone metastasis.


Gastrointestinal stromal tumor Bone metastasis Mutation DOG1 KIT PDGFRA 



The molecular studies and DOG1 staining were performed in Ankara University, Department of Pathology, and supported by an institutional contribution of TUBITAK (project no.: 209S109).

This study presented as poster at the USCAP Meeting, Baltimore, USA, 2013.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2017_2138_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 22 kb)


  1. 1.
    Weiss SW, Goldblum JR, Enzinger FM (2008) Enzinger and Weiss’ soft tissue tumors, 5th edn. Mosby Elsevier, PhiladelphiaGoogle Scholar
  2. 2.
    Bertulli R, Fumagalli E, Coco P, Messina A, Morosi C, Dileo P, Casali PG (2009) Unusual metastatic sites in gastrointestinal stromal tumor (GIST). J Clin Oncol 27:15s (suppl; abstr 10566)CrossRefGoogle Scholar
  3. 3.
    Schuler M, Zeile M, Pink D, Tunn P, Kretzschmar A, Rau B, P. R (2008) Incidence of bone metastases in GIST: a single center analysis of 307 patients with metastatic disease. J Clin Oncol 26:15s (suppl; abstr 10565)Google Scholar
  4. 4.
    Burkill GJ, Badran M, Al-Muderis O, Meirion Thomas J, Judson IR, Fisher C, Moskovic EC (2003) Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology 226(2):527–532CrossRefPubMedGoogle Scholar
  5. 5.
    Stamatakos M, Douzinas E, Stefanaki C, Safioleas P, Polyzou E, Levidou G, Safioleas M (2009) Gastrointestinal stromal tumor. World J Surg Oncol 7:61. doi: 10.1186/1477-7819-7-61 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Corless CL (2014) Gastrointestinal stromal tumors: what do we know now? Mod Pathol 27(Suppl 1):S1–16. doi: 10.1038/modpathol.2013.173 CrossRefPubMedGoogle Scholar
  7. 7.
    Maleddu A, Pantaleo MA, Nannini M, Biasco G (2011) The role of mutational analysis of KIT and PDGFRA in gastrointestinal stromal tumors in a clinical setting. J Transl Med 9:75. doi: 10.1186/1479-5876-9-75 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lasota J, Corless CL, Heinrich MC, Debiec-Rychter M, Sciot R, Wardelmann E, Merkelbach-Bruse S, Schildhaus HU, Steigen SE, Stachura J, Wozniak A, Antonescu C, Daum O, Martin J, Del Muro JG, Miettinen M (2008) Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases. Mod Pathol 21(4):476–484. doi: 10.1038/modpathol.2008.2 CrossRefPubMedGoogle Scholar
  9. 9.
    Lasota J, Miettinen M (2008) Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 53(3):245–266. doi: 10.1111/j.1365-2559.2008.02977.x CrossRefPubMedGoogle Scholar
  10. 10.
    Slimack NP, Liu JC, Koski T, McClendon J Jr, O’Shaughnessy BA (2012) Metastatic gastrointestinal stromal tumor to the thoracic and lumbar spine: first reported case and surgical treatment. Spine J 12(1):e7–12. doi: 10.1016/j.spinee.2011.10.037 CrossRefPubMedGoogle Scholar
  11. 11.
    Policarpio-Nicolas ML, Lal A, Nicolas MM, De Frias DV, Nayar R, Nemcek AL Jr, Mellott AL (2006) Bone metastasis of a gastrointestinal tumor with diagnosis by fine needle aspiration biopsy. Acta Cytol 50(3):354–357PubMedGoogle Scholar
  12. 12.
    Ozan E, Oztekin O, Alacacioglu A, Aykas A, Postaci H, Adibelli Z Esophageal gastrointestinal stromal tumor with pulmonary and bone metastases. Diagn Interv Radiol 16(3):217–220. doi: 10.4261/1305-3825.DIR.1861-08.2
  13. 13.
    Jati A, Tatli S, Morgan JA, Glickman JN, Demetri GD, Van den Abbele A, Silverman SG (2012) Imaging features of bone metastases in patients with gastrointestinal stromal tumors. Diagn Interv Radiol. doi: 10.4261/1305-3825.dir.5179-11.1 PubMedGoogle Scholar
  14. 14.
    Gil-Arnaiz I, Martinez-Trufero J, Pazo-Cid RA, Felipo F, Lecumberri MJ, Calderero V (2009) Skull metastasis from rectal gastrointestinal stromal tumours. Clin Transl Oncol 11(9):625–627CrossRefPubMedGoogle Scholar
  15. 15.
    Di Scioscio V, Greco L, Pallotti MC, Pantaleo MA, Maleddu A, Nannini M, Bazzocchi A, Di Battista M, Mandrioli A, Lolli C, Saponara M, Giorgio G, Biasco G, Zompatori M (2011) Three cases of bone metastases in patients with gastrointestinal stromal tumors. Rare Tumors 3(2):e17. doi: 10.4081/rt.2011.e17 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chu TYC, Wong CS (2009) Bone metastases from gastrointestinal stromal tumour: correlation with positron emission tomography–computed tomography. J HK Coll Radiol 11:172–175Google Scholar
  17. 17.
    Chou SQH, Tse KS, Wong WK, Chan SCH (2010) Vulval gastrointestinal stromal tumours with bone metastases. J Hong Kong Col Radiol 13:88–90Google Scholar
  18. 18.
    Bajel A, Simpson I, Longano A, Roy S, Richardson G (2009) Bone marrow metastasis in gastro-intestinal stromal tumour. Br J Haematol 147(1):2. doi: 10.1111/j.1365-2141.2009.07735.x CrossRefPubMedGoogle Scholar
  19. 19.
    Abuzakhm SM, Acre-Lara CE, Zhao W, Hitchcock C, Mohamed N, Arbogast D, Shah MH (2011) Unusual metastases of gastrointestinal stromal tumor and genotypic correlates: case report and review of the literature. J Gastrointest Oncol 2:45–49PubMedPubMedCentralGoogle Scholar
  20. 20.
    Baeg MK, Bae SH, Lee KH, Kim J, Park IS, Jin JY Diplopia as a presenting symptom in a gastric gastrointestinal stromal tumor. Jpn J Clin Oncol 41(2):265–268. doi: 10.1093/jjco/hyq176
  21. 21.
    Jain A, Dubashi B, Chandra SS, Halanaik D (2011) Mesentric gastrointestinal stromal tumor with bone metastases. Indian J Cancer 48(3):383–384. doi: 10.4103/0019-509X.84934 CrossRefPubMedGoogle Scholar
  22. 22.
    Tezcan Y, Koc M (2011) Gastrointestinal stromal tumor of the rectum with bone and liver metastasis: a case study. Med Oncol 28(Suppl 1):S204–S206. doi: 10.1007/s12032-010-9697-7 CrossRefPubMedGoogle Scholar
  23. 23.
    Selcukbiricik F, Tural D, Oztürk MA, Dervisoglu D, Sager S, Hiz M, Mandel NM (2012) Gastrointestinal stromal tumor of the rectum with scapular metastasis: a case report. J Med Case Rep 6(145). doi: 10.1186/1752-1947-6-145
  24. 24.
    Steigen SE, Eide TJ (2009) Gastrointestinal stromal tumors (GISTs): a review. APMIS 117(2):73–86. doi: 10.1111/j.1600-0463.2008.00020.x CrossRefPubMedGoogle Scholar
  25. 25.
    Miettinen M, Sobin LH, Lasota J (2009) Gastrointestinal stromal tumors presenting as omental masses—a clinicopathologic analysis of 95 cases. Am J Surg Pathol 33(9):1267–1275. doi: 10.1097/PAS.0b013e3181a13e99 CrossRefPubMedGoogle Scholar
  26. 26.
    Miettinen M, Makhlouf H, Sobin LH, Lasota J (2006) Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol 30(4):477–489CrossRefPubMedGoogle Scholar
  27. 27.
    Miettinen M, Sobin LH, Lasota J (2005) 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 29(1):52–68CrossRefPubMedGoogle Scholar
  28. 28.
    Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J (2001) 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 25(9):1121–1133CrossRefPubMedGoogle Scholar
  29. 29.
    DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF (2000) Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231(1):51–58CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yoshikawa H, Myoui A, Ochi T, Araki N, Ueda T, Kudawara I, Nakanishi K, Tanaka H, Nakamura H (1999) Bone metastases from soft tissue sarcomas. Semin Musculoskelet Radiol 3(2):183–190. doi: 10.1055/s-2008-1080061 CrossRefPubMedGoogle Scholar
  31. 31.
    Blay JY, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, Emile JF, Gronchi A, Hogendoorn PC, Joensuu H, Le Cesne A, McClure J, Maurel J, Nupponen N, Ray-Coquard I, Reichardt P, Sciot R, Stroobants S, van Glabbeke M, van Oosterom A, Demetri GD (2005) Panelists Gcm: consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol 16(4):566–578. doi: 10.1093/annonc/mdi127 CrossRefPubMedGoogle Scholar
  32. 32.
    Aras Y, Akcakaya MO, Unal SN, Bilgic B, Unal OF (2012) Bone marrow necrosis secondary to imatinib usage, mimicking spinal metastasis on magnetic resonance imaging and FDG-PET/CT. J Neurosurg Spine 16(1):57–60. doi: 10.3171/2011.9.SPINE11401 CrossRefPubMedGoogle Scholar
  33. 33.
    Vanel D, Bonvalot S, Pechoux CL, Cioffi A, Domont J, Cesne AL (2007) Imatimid-induced bone marrow necrosis detected on MRI examination and mimicking bone metastases. Skelet Radiol 36(9):895–898. doi: 10.1007/s00256-007-0344-0 CrossRefGoogle Scholar
  34. 34.
    Reith JD, Goldblum JR, Lyles RH, Weiss SW (2000) Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 13(5):577–585. doi: 10.1038/modpathol.3880099 CrossRefPubMedGoogle Scholar
  35. 35.
    Yamamoto H, Oda Y, Kawaguchi K, Nakamura N, Takahira T, Tamiya S, Saito T, Oshiro Y, Ohta M, Yao T, Tsuneyoshi M (2004) c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol 28(4):479–488CrossRefPubMedGoogle Scholar
  36. 36.
    Barros A, Linhares E, Valadao M, Goncalves R, Vilhena B, Gil C, Ramos C (2011) Extragastrointestinal stromal tumors (EGIST): a series of case reports. Hepato-Gastroenterology 58(107–108):865–868PubMedGoogle Scholar
  37. 37.
    Miettinen M, Lasota J (2011) Histopathology of gastrointestinal stromal tumor. J Surg Oncol 104(8):865–873. doi: 10.1002/jso.21945 CrossRefPubMedGoogle Scholar
  38. 38.
    Molina I, Seamon LG, Copeland LJ, Suarez A (2009) Reclassification of leiomyosarcoma as an extra-gastrointestinal stromal tumor of the gynecologic tract. Int J Gynecol Pathol 28(5):458–463. doi: 10.1097/PGP.0b013e31819c7fc1 CrossRefPubMedGoogle Scholar
  39. 39.
    Foster R, Solano S, Mahoney J, Fuller A, Oliva E, Seiden MV (2006) Reclassification of a tubal leiomyosarcoma as an eGIST by molecular evaluation of c-KIT. Gynecol Oncol 101(2):363–366. doi: 10.1016/j.ygyno.2005.12.022 CrossRefPubMedGoogle Scholar
  40. 40.
    Weppler EH, Gaertner EM (2005) Malignant extragastrointestinal stromal tumor presenting as a vaginal mass: report of an unusual case with literature review. Int J Gynecol Cancer 15(6):1169–1172. doi: 10.1111/j.1525-1438.2005.00269.x CrossRefPubMedGoogle Scholar
  41. 41.
    Lam MM, Corless CL, Goldblum JR, Heinrich MC, Downs-Kelly E, Rubin BP (2006) Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: a diagnostic pitfall. Int J Gynecol Pathol 25(3):288–292. doi: 10.1097/01.pgp.0000215291.22867.18 CrossRefPubMedGoogle Scholar
  42. 42.
    De Chiara A, De Rosa V, Lastoria S, Franco R, Botti G, Iaffaioli VR, Apice G (2006) Primary gastrointestinal stromal tumor of the liver with lung metastases successfully treated with STI-571 (imatinib mesylate). Front Biosci 11:498–501CrossRefPubMedGoogle Scholar
  43. 43.
    Hu X, Forster J, Damjanov I (2003) Primary malignant gastrointestinal stromal tumor of the liver. Arch Pathol Lab Med 127(12):1606–1608. doi: 10.1043/1543-2165(2003)127<1606:PMGSTO>2.0.CO;2 PubMedGoogle Scholar
  44. 44.
    Luo XL, Liu D, Yang JJ, Zheng MW, Zhang J, Zhou XD (2009) Primary gastrointestinal stromal tumor of the liver: a case report. World J Gastroenterol 15(29):3704–3707CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ochiai T, Sonoyama T, Kikuchi S, Ikoma H, Kubota T, Nakanishi M, Ichikawa D, Kikuchi S, Fujiwara H, Okamoto K, Sakakura C, Kokuba Y, Taniguchi H, Otsuji E (2009) Primary large gastrointestinal stromal tumor of the liver: report of a case. Surg Today 39(7):633–636. doi: 10.1007/s00595-008-3885-5 CrossRefPubMedGoogle Scholar
  46. 46.
    Yamamoto H, Miyamoto Y, Nishihara Y, Kojima A, Imamura M, Kishikawa K, Takase Y, Ario K, Oda Y, Tsuneyoshi M (2010) Primary gastrointestinal stromal tumor of the liver with PDGFRA gene mutation. Hum Pathol 41(4):605–609. doi: 10.1016/j.humpath.2009.09.016 CrossRefPubMedGoogle Scholar
  47. 47.
    Merten L, Agaimy A, Moskalev EA, Giedl J, Kayser C, Geddert H, Schaefer IM, Cameron S, Werner M, Strobel P, Hartmann A, Haller F (2016) Inactivating mutations of RB1 and TP53 correlate with sarcomatous histomorphology and metastasis/recurrence in gastrointestinal stromal tumors. Am J Clin Pathol 146(6):718–726. doi: 10.1093/ajcp/aqw193 CrossRefPubMedGoogle Scholar
  48. 48.
    Wong NA (2011) Gastrointestinal stromal tumours—an update for histopathologists. Histopathology 59(5):807–821. doi: 10.1111/j.1365-2559.2011.03812.x CrossRefPubMedGoogle Scholar
  49. 49.
    Miettinen M, Lasota J (2005) KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 13(3):205–220CrossRefPubMedGoogle Scholar
  50. 50.
    Miettinen M, Wang ZF, Lasota J (2009) DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases. Am J Surg Pathol 33(9):1401–1408. doi: 10.1097/PAS.0b013e3181a90e1a CrossRefPubMedGoogle Scholar
  51. 51.
    Corless CL, McGreevey L, Town A, Schroeder A, Bainbridge T, Harrell P, Fletcher JA, Heinrich MC (2004) KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors. J Mol Diagn 6(4):366–370. doi: 10.1016/S1525-1578(10)60533-8 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Lee JR, Joshi V, Griffin JW Jr, Lasota J, Miettinen M (2001) Gastrointestinal autonomic nerve tumor: immunohistochemical and molecular identity with gastrointestinal stromal tumor. Am J Surg Pathol 25(8):979–987CrossRefPubMedGoogle Scholar
  53. 53.
    Heinrich MC, Maki RG, Corless CL, Antonescu CR, Harlow A, Griffith D, Town A, McKinley A, Ou WB, Fletcher JA, Fletcher CD, Huang X, Cohen DP, Baum CM, Demetri GD (2008) Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 26(33):5352–5359. doi: 10.1200/JCO.2007.15.7461 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Martin J, Poveda A, Llombart-Bosch A, Ramos R, Lopez-Guerrero JA, Garcia del Muro J, Maurel J, Calabuig S, Gutierrez A, Gonzalez de Sande JL, Martinez J, De Juan A, Lainez N, Losa F, Alija V, Escudero P, Casado A, Garcia P, Blanco R, Buesa JM (2005) Spanish Group for Sarcoma R: 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 23(25):6190–6198. doi: 10.1200/JCO.2005.19.554 CrossRefPubMedGoogle Scholar
  55. 55.
    Ma Y, Cunningham ME, Wang X, Ghosh I, Regan L, Longley BJ (1999) Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region. J Biol Chem 274(19):13399–13402CrossRefPubMedGoogle Scholar
  56. 56.
    Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M, Maki R, Brennan MF, Ladanyi M, DeMatteo RP, Besmer P (2003) 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 9(9):3329–3337PubMedGoogle Scholar
  57. 57.
    Kontogianni-Katsarou K, Dimitriadis E, Lariou C, Kairi-Vassilatou E, Pandis N, Kondi-Paphiti A (2008) KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential. World J Gastroenterol 14(12):1891–1897CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Joensuu H, Rutkowski P, Nishida T, Steigen SE, Brabec P, Plank L, Nilsson B, Braconi C, Bordoni A, Magnusson MK, Sufliarsky J, Federico M, Jonasson JG, Hostein I, Bringuier PP, Emile JF (2015) KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence. J Clin Oncol 33(6):634–642. doi: 10.1200/JCO.2014.57.4970 CrossRefPubMedGoogle Scholar
  59. 59.
    Patrikidou A, Domont J, Chabaud S, Ray-Coquard I, Coindre JM, Bui-Nguyen B, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Perol D, Emile JF, Blay JY, Le Cesne A, French Sarcoma G (2016) Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group. Eur J Cancer 52:173–180. doi: 10.1016/j.ejca.2015.10.069 CrossRefPubMedGoogle Scholar
  60. 60.
    Kumari N, Priyaa V, Shukla P, Kumar A, Aggarwal R, Krishnani N (2016) Gastrointestinal stromal tumor: genotype frequency and prognostic relevance. Appl Immunohistochem Mol Morphol. doi: 10.1097/PAI.0000000000000395 PubMedGoogle Scholar
  61. 61.
    Wang HC, Li TY, Chao YJ, Hou YC, Hsueh YS, Hsu KH, Shan YS (2016) KIT exon 11 codons 557-558 deletion mutation promotes liver metastasis through the CXCL12/CXCR4 axis in gastrointestinal stromal tumors. Clin Cancer Res 22(14):3477–3487. doi: 10.1158/1078-0432.CCR-15-2748 CrossRefPubMedGoogle Scholar
  62. 62.
    Rossle M, Hirschmann A, Diebold J (2011) Mutational spectrum and therapy response of metastasized GIST in Central Switzerland—a population-based study. Eur J Cancer 47(9):1305–1311. doi: 10.1016/j.ejca.2011.01.012 CrossRefPubMedGoogle Scholar
  63. 63.
    Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11(11):4182–4190. doi: 10.1158/1078-0432.CCR-04-2245 CrossRefPubMedGoogle Scholar
  64. 64.
    Wardelmann E, Merkelbach-Bruse S, Pauls K, Thomas N, Schildhaus HU, Heinicke T, Speidel N, Pietsch T, Buettner R, Pink D, Reichardt P, Hohenberger P (2006) Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res 12(6):1743–1749. doi: 10.1158/1078-0432.CCR-05-1211 CrossRefPubMedGoogle Scholar
  65. 65.
    Saponara M, Urbini M, Astolfi A, Indio V, Ercolani G, Del Gaudio M, Santini D, Pirini MG, Fiorentino M, Nannini M, Lolli C, Mandrioli A, Gatto L, Brandi G, Biasco G, Pinna AD, Pantaleo MA (2015) Molecular characterization of metastatic exon 11 mutant gastrointestinal stromal tumors (GIST) beyond KIT/PDGFRalpha genotype evaluated by next generation sequencing (NGS). Oncotarget 6(39):42243–42257. doi: 10.18632/oncotarget.6278 PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Kemal Kosemehmetoglu
    • 1
  • Gulsah Kaygusuz
    • 2
  • Karen Fritchie
    • 3
  • Ovgu Aydin
    • 4
  • Ozlem Yapicier
    • 5
  • Oznur Coskun
    • 2
  • Ersin Karatayli
    • 6
  • Senay Boyacigil
    • 2
  • Gulnur Guler
    • 7
  • Sergulen Dervisoglu
    • 4
  • Isinsu Kuzu
    • 2
  1. 1.Department of PathologyHacettepe University School of MedicineAnkaraTurkey
  2. 2.Department of PathologyAnkara University School of MedicineAnkaraTurkey
  3. 3.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  4. 4.Department of PathologyIstanbul University Cerrahpasa School of MedicineIstanbulTurkey
  5. 5.Department of PathologyAcıbadem University School of MedicineIstanbulTurkey
  6. 6.Hepatology InstituteAnkara UniversityAnkaraTurkey
  7. 7.AnkaraTurkey

Personalised recommendations