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Clinical and prognostic value of mutational status in patients with gastrointestinal stromal tumors

Abstract

Mutational status of GIST patients plays an important role in clinical practice. Gastrointestinal stromal tumors are the most frequent mesenchymal tumors that are characterized by mutations in tyrosine kinase receptors KIT and PDGFRA. Mutations in KIT and PDGFRA genes determine the sensitivity to therapy with tyrosine kinase inhibitors and are associated with prognosis of GIST patients. Analysis of the mutational status of 52 GIST patients with localized disease treated in N.N. Blokhin RCRC between 2001 and 2007 was conducted. KITmutations were found in 40 patients (76,9%), of which 34 cases (65,5%) exhibited 11 exon, 5 (9,6%) 9 exon and 1 (1,9%) case 13 exon. PDGFRA mutations were detected in 18 exon in 7 (13,5%) patients. WT genotype was found in 5 (9,6%) patients. Deletions in KIT exon 11 were detected in 17 c10 better clinical outcome (5-year survival rate of 100,0% and 75,0%) when compared with deletions in KIT exone 11 and duplications in exon 9 (5-year survival rate of 48,4% and 25,0%). Survival analysis with deletions KIT11 exon showed no significant difference of survival rate in patients with gastric and intestinal stromal tumors.

About the Authors

P. P. Arkhiri
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


N. Ts. Tsymgitova
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


I. S. Stilidi
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


I. V. Poddubnaya
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


M. P. Nikulin
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


I. V. Tsyganova
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


O. A. Anurova
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


N. N. Mazurenko
FGBU N.N. Blokhin Russian Cancer Research Center
Russian Federation


References

1. Беляков И.С., Анурова О.А., Снигур П.В., Цыганова И.В., Сельчук В.Ю., Мазуренко Н.Н. Мутации генов с-Kit и PDGFRA и клинико-морфологические особенности стромальных опухолей желудочно-кишечного тракта. Вопр. Онкол. 2007, т. 53, № 6, с. 677-681.

2. Снигур П.В., Анурова О.А., Петровичев Н.Н., Сельчук В.Ю. Клинико-морфологические особенности стромальных опухолей ЖКТ. Вопр. Онкол. 2003, т. 49, № 6, с. 705-710.

3. Цыганова И.В., Анурова О.А., Мазуренко Н.Н. Морфологические особенности и критерии прогноза стромальных опухолей ЖКТ. Архив патологии. 2011, т. 73, № 6, с. 37-42.

4. Мазуренко Н.Н., Беляков И.С., Цыганова И.В., Гагарин И.М., Анурова О.А. Значение молекулярно-генетических маркеров для прогноза и лечения стромальных опухолей ЖКТ. Достижения и перспективы лекарственного лечения злокачественных опухолей. Этюды химиотерапии III. Под ред. В.А. Горбуновой. М., «Фармарус Принт Медиа». 2011, с. 111-126.

5. Andersson J., Bumming P., Meis-Kindblom J.M. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology. 2006, v. 130, p. 1573-1581.

6. Andersson J., Sjogren H., Meis-Kindblom J.M., Stenman G., Aman P., Kindblom L.G. The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. Am. J. Pathol. 2002, v. 160, p. 15-22.

7. Antonescu C.R., Sommer G., Sarran L. 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, No. 9, p. 3329-3337.

8. Cho S., Kitadai Y., Yoshida S. 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, v. 28, p. 1361-1367.

9. Corless C.L., Schroeder A., Griffith D. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J. Clin. Oncol. 2005, v. 23, p. 5357-5364.

10. Corless C.L., Schroeder A., Griffith D. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J. Clin. Oncol. 2005, No. 23, p. 5357-5364.

11. De Matteo R.P., Lewis J.J., Leung D., Mudan S.S., Woodruff J.M., Brennan M.F. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann. Surg. 2000, v. 231, p. 51-58.

12. Demetri G.D. GRID Trial: Regorafenib Shows Promise for Patients with GIST. ASCO 2012, A. LBA10008.

13. Demetri G.D., Heinrich M.C., Fletcher J.A. et al. Molecular Target Modulation, Imaging, and Clinical Evaluation of Gastrointestinal Stromal Tumor Patients Treated with Sunitinib Malate after Imatinib Failure. Clin. Cancer Res. 2009, No. 15, v. 18, p. 5902-5909.

14. Demetri G.D. Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). Eur. J. Cancer. 2002, v. 38 (Suppl. 5), p. 52-59.

15. Duensing A., Medeiros F., McConarty B. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene. 2004, v. 23, p. 3999-4006.

16. Fletcher J.A., Corless C.L., Dimitrijevic S. Mechanisms of resistance to imatinib mesylate in advanced gastrointestinal stromal tumors. Am. Soc. Clin. Oncol. 2003, v. 22, p. 815 (A3275).

17. Fletcher J.A. Role ofKIT and platelet-derived growth factor receptors as oncoproteins. Semin. Oncol. 2004, v. 31, Suppl. 6, p. 4-11.

18. Heinrich M.C., Corless C.L., Duensing A. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003, v. 299, p. 708-710.

19. Hirota S., Nishida T., Isozaki K. Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumors. J. Pathol. 2001, v. 193, p. 505-510.

20. Lasota J., Wozniak A., Sarlomo-Rikala M. 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, v. 157, p. 1091-1095.

21. Lasota J., Dansonka-Mieszkowska A., Stachura T., Gastrointestinal stromal tumors with internal tandem duplications in 3end of KIT juxtamembrane domain occur predominantly in stomach and generally seem to have a favorable outcome. Mod. Pathol. 2003, v. 16, p. 1257-1264.

22. Lasota J., Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin. Diagn. Pathol. 2006, v. 23, p. 91-102.

23. Martin J., Poveda J., Llombart-Bosch A. 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, v. 23, p. 6190-6198.

24. Miettinen M., Lasota J. Gastrointestinal Stromal Tumors. Review on Morphology, Molecular Pathology, Prognosis, and Differential Diagnosis. Arch. Pathol. Lab. Med. 2006, No. 130, p. 1466-1476.

25. Wardelmann E., Hrychyk A., Markelbach-Bruse S.J. Association of platelet-derived growth factor receptor a mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors. Mol. Diagn. 2004, No. 6, p. 197-204.

26. Demetri G.D., von Mehren M., Blanke C.D.N. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. Engl. J. Med. 2002, v. 347, p. 472-480.

27. Joensuu H. Sunitinib for imatinib-resistant GIST. The Lancet. 2006, v. 368, No. 9544, p. 1303-1304.


Review

For citations:


Arkhiri P.P., Tsymgitova N.Ts., Stilidi I.S., Poddubnaya I.V., Nikulin M.P., Tsyganova I.V., Anurova O.A., Mazurenko N.N. Clinical and prognostic value of mutational status in patients with gastrointestinal stromal tumors. Bone and soft tissue sarcomas, tumors of the skin. 2013;(1):42-46. (In Russ.)

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ISSN 2219-4614 (Print)
ISSN 2782-3687 (Online)