Skip to main content
Top
Published in: Langenbeck's Archives of Surgery 6/2006

01-11-2006 | Case Management and Clinical Consequences

Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during imatinib mesylate treatment

Authors: Chun-Nan Yeh, Tsung-Wen Chen, Feng-Yuan Liu, Yi-Yin Jan, Miin-Fu Chen

Published in: Langenbeck's Archives of Surgery | Issue 6/2006

Login to get access

Abstract

Purpose

Imatinib mesylate showed a sustained objective response in patients with advanced gastrointestinal stromal tumors (GISTs) since its introduction in 2001. Here we reported genetic changes during imatinib mesylate treatment especially when the patient had partial response or stationary disease.

Materials and methods

Between 2001 and June 2005, 44 advanced GIST patients were treated with imatinib mesylate. Among them, five patients (11.9%) (four with partial response and one with stationary disease) received surgical treatment during imatinib mesylate treatment. We compared the genetic status of each tumor in the five patients before and after imatinib mesylate treatment.

Results

Symptomatic gallbladder stone with or without cholecystitis (two patients), lower GI bleeding (one patient), upper GI bleeding (one patient), and enterocutaneous fistula (one patient) comprised the indications for operation. Before imatinib mesylate treatment, four of the five patients displayed deletion mutation and one patient displayed point mutation in exon 11. After treatment, one patient developed second novel missense mutation in exon 17 with acquired resistance since he was administered with only half dose of imatinib mesylate. The other four patients taking the same dose of imatinib mesylate exhibited identical mutation to the previous lesions.

Conclusions

Necrosis of large and bulky tumors after imatinib mesylate therapy might be the reason of gastrointestinal hemorrhage and enterocutaneous fistula requiring surgical intervention. Imatinib mesylate could induce acquired resistance during treatment and second novel mutation might be the reason.
Literature
1.
go back to reference Lewis JJ, Brennan MF (1996) Soft tissue sarcomas. Curr Prob Surg 33(10):817–872CrossRef Lewis JJ, Brennan MF (1996) Soft tissue sarcomas. Curr Prob Surg 33(10):817–872CrossRef
2.
go back to reference Rossi CR, Mocellin S, Mencarelli R, Foletto M, Pilati P, Nitti D, Lise M (2003) Gastrointestinal stromal tumors: from a surgical to a molecular approach. Int J Cancer 107:171–176PubMedCrossRef Rossi CR, Mocellin S, Mencarelli R, Foletto M, Pilati P, Nitti D, Lise M (2003) Gastrointestinal stromal tumors: from a surgical to a molecular approach. Int J Cancer 107:171–176PubMedCrossRef
3.
go back to reference 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 231:51–58PubMedCrossRef 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 231:51–58PubMedCrossRef
4.
go back to reference Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998) Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259–1269PubMed Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998) Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259–1269PubMed
5.
go back to reference Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH (1999) Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 23:377–389PubMedCrossRef Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH (1999) Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 23:377–389PubMedCrossRef
6.
go back to reference Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD (2001) Effect of tyrosine kinase inhibitor DTI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056PubMedCrossRef Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD (2001) Effect of tyrosine kinase inhibitor DTI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056PubMedCrossRef
7.
go back to reference Akwari OE, Dozois RR, Weiland LH, Bearhrs OH (1978) Leiomyosarcoma of the small and large bowel. Cancer 42:1375–1384PubMedCrossRef Akwari OE, Dozois RR, Weiland LH, Bearhrs OH (1978) Leiomyosarcoma of the small and large bowel. Cancer 42:1375–1384PubMedCrossRef
8.
go back to reference Shiu MH, Farr GH, Papchristou DN, Hajdu SI (1982) Myosarcomas of the stomach: nature history, prognostic factors and management. Cancer 49:177–187PubMedCrossRef Shiu MH, Farr GH, Papchristou DN, Hajdu SI (1982) Myosarcomas of the stomach: nature history, prognostic factors and management. Cancer 49:177–187PubMedCrossRef
9.
go back to reference McGrath PC, Neifeld JP, Lawrence W Jr, Kay S, Horsley JS 3rd, Parker GA (1987) Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg 206:706–710PubMedCrossRef McGrath PC, Neifeld JP, Lawrence W Jr, Kay S, Horsley JS 3rd, Parker GA (1987) Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg 206:706–710PubMedCrossRef
10.
go back to reference Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM Prognostic factors influencing survival in gastrointestinal leiomyosarcoma. Implications for surgical management and staging. Ann Surg 215:68–77 Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM Prognostic factors influencing survival in gastrointestinal leiomyosarcoma. Implications for surgical management and staging. Ann Surg 215:68–77
11.
go back to reference Goss GA, Merriam P, Manola A (2000) Clinical and pathological characteristics of gastrointestinal stromal tumors (GIST). Prog Proc Am Soc Clin Oncol 19:559a. abstract Goss GA, Merriam P, Manola A (2000) Clinical and pathological characteristics of gastrointestinal stromal tumors (GIST). Prog Proc Am Soc Clin Oncol 19:559a. abstract
12.
go back to reference Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosin kinase on the growth of Bcr–Abl positive cells. Nat Med 2:561–566PubMedCrossRef Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosin kinase on the growth of Bcr–Abl positive cells. Nat Med 2:561–566PubMedCrossRef
13.
go back to reference Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB (2000) Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295:139–145PubMed Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB (2000) Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295:139–145PubMed
14.
go back to reference Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ (2000) Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96:925–932PubMed Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ (2000) Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96:925–932PubMed
15.
go back to reference Wang WL, Healy ME, Sattler M, Verma S, Lin J, Maulik G, Stiles CD, Griffin JD, Johnson BE, Salgia R (2000) Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571. Oncogene 19:3521–3528PubMedCrossRef Wang WL, Healy ME, Sattler M, Verma S, Lin J, Maulik G, Stiles CD, Griffin JD, Johnson BE, Salgia R (2000) Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571. Oncogene 19:3521–3528PubMedCrossRef
16.
go back to reference Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(7):472–480PubMedCrossRef Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(7):472–480PubMedCrossRef
17.
go back to reference Yeh CN, Chen TW, Wu TJ, Hsueh S, Jan YY (2006) Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: implications of imatinib mesylate. World J Gastroenterol 12(23):3760–3765PubMed Yeh CN, Chen TW, Wu TJ, Hsueh S, Jan YY (2006) Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: implications of imatinib mesylate. World J Gastroenterol 12(23):3760–3765PubMed
18.
go back to reference Green S, Weiss GR (1992) Southwest Oncology Group standard response criteria, end point definitions and toxicity criteria. Invest New Drugs 10:239–253PubMedCrossRef Green S, Weiss GR (1992) Southwest Oncology Group standard response criteria, end point definitions and toxicity criteria. Invest New Drugs 10:239–253PubMedCrossRef
19.
go back to reference Cancer Therapy Evaluation Program (1999) Common toxicity criteria manual: common toxicity criteria, version 2.0. Bethesda, MD: National Cancer Institute, June Cancer Therapy Evaluation Program (1999) Common toxicity criteria manual: common toxicity criteria, version 2.0. Bethesda, MD: National Cancer Institute, June
20.
go back to reference Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342–4349PubMedCrossRef Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342–4349PubMedCrossRef
21.
go back to reference Debiec-Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, Vranckx H, Wasag B, Prenen H, Roesel J, Hagemeijer A, Van Oosterom A et al (2005) Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 128(2):270–279PubMedCrossRef Debiec-Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, Vranckx H, Wasag B, Prenen H, Roesel J, Hagemeijer A, Van Oosterom A et al (2005) Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 128(2):270–279PubMedCrossRef
22.
go back to reference Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W, Raymond AK, Prieto VG, Oyedeji CO, Hunt KK, Pollock RE, Feig BW et al (2004) A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 64(17):5913–5919PubMedCrossRef Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W, Raymond AK, Prieto VG, Oyedeji CO, Hunt KK, Pollock RE, Feig BW et al (2004) A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 64(17):5913–5919PubMedCrossRef
23.
go back to reference Tamborini E, Bonadiman L, Greco A, Albertini V, Negri T, Gronchi A, Bertulli R, Colecchia M, Casali PG, Pierotti MA, Pilotti S (2004) A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 127(1):294–299PubMedCrossRef Tamborini E, Bonadiman L, Greco A, Albertini V, Negri T, Gronchi A, Bertulli R, Colecchia M, Casali PG, Pierotti MA, Pilotti S (2004) A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 127(1):294–299PubMedCrossRef
24.
go back to reference Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC (2005) PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23(23): 5357–5364PubMedCrossRef Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC (2005) PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23(23): 5357–5364PubMedCrossRef
25.
go back to reference Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG et al (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11(11):4182–4190PubMedCrossRef Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG et al (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11(11):4182–4190PubMedCrossRef
26.
go back to reference Bertucci F, Goncalves A, Monges G, Madroszyk A, Guiramand J, Moutardier V, Noguchi T, Dubreuil P, Sobol H (2006) Acquired resistance to imatinib and secondary KIT exon 13 mutation in gastrointestinal stromal tumour. Oncol Rep 16(1):97–101PubMed Bertucci F, Goncalves A, Monges G, Madroszyk A, Guiramand J, Moutardier V, Noguchi T, Dubreuil P, Sobol H (2006) Acquired resistance to imatinib and secondary KIT exon 13 mutation in gastrointestinal stromal tumour. Oncol Rep 16(1):97–101PubMed
Metadata
Title
Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during imatinib mesylate treatment
Authors
Chun-Nan Yeh
Tsung-Wen Chen
Feng-Yuan Liu
Yi-Yin Jan
Miin-Fu Chen
Publication date
01-11-2006
Publisher
Springer-Verlag
Published in
Langenbeck's Archives of Surgery / Issue 6/2006
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI
https://doi.org/10.1007/s00423-006-0103-z

Other articles of this Issue 6/2006

Langenbeck's Archives of Surgery 6/2006 Go to the issue