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Vol. 66 No. 8: Issue 8

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Oncogene mutational analysis in imatinib naive population of gastrointestinal stromal tumor patients

https://doi.org/10.14715/cmb/2020.66.8.5
Abdul Wahab Ali Abuderman
Department of Basic Medical Science, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Postal Code:11942, Saudi Arabia
Fahad M. Aldakheel
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia

Corresponding Author(s) : Fahad M. Aldakheel

faldakheel@ksu.edu.sa

Cellular and Molecular Biology, Vol. 66 No. 8: Issue 8

Abstract

There are very scanty reports on gastro-intestinal stromal tumors (GISTs), a very common tumor of mesenchymal cells in GIT track primary resistance to imatinib. This comprehensive study identifies the prevalence, clinical presentation and GIST genotype association in the imatinib naí¯ve population. Prospectively a record of anthropometric, baseline demographic data and clinical details for the patients diagnosed with GIST were scrutinized. Pathological information included the presence or absence of necrosis, tumor size, mitotic counts, immune-histochemical staining for CD 34, CD 117 and DOG1 was performed using biopsy sample. Selected exon genes of KIT, PDGFRA and BRAF were amplified and subjected to mutation analysis by direct sequencing. Appropriate statistical analyses were performed. The male/female ratio was 1.8:1 among 54 patients with GIST. The mean GIST size was comparatively bigger in females (2.49±0.855) than males (2.26±1.13). The stomach was the most common site for GIST followed by the Small bowel and rectum. The majority of the tumours were spindle cell. This study reports 12 different types of mutation among 39 KIT, 8 PDGFRA and 7 BRAF mutations. In KIT, the most prevalent was exon 11 mutation with the KITdelinc557/558 (14/30) being the major exon 11 type mutation. In PDGRFA, five exons 18 with p.D842V substitution and three exons 12 deletion mutation was reported. Seven patients had strong or diffuse BRAF staining having V600E type mutation as major BRAF type mutation. Drug-resistant GIST due to acquired mutations remains a serious issue, therefore genetic information of such mutational related to drug-resistant may provide the imperative clue for diagnosis and clinical treatment. These mutations are pivotal for prognosis and associated with imatinib as not all of them but only a few are reported resistant to the imatinib.

Keywords

Gastrointestinal stromal tumors (GISTs) Imatinib Mutation KIT PDGRFA BRAF.
Ali Abuderman, A. W., & M. Aldakheel, F. (2020). Oncogene mutational analysis in imatinib naive population of gastrointestinal stromal tumor patients. Cellular and Molecular Biology, 66(8), 26–32. https://doi.org/10.14715/cmb/2020.66.8.5
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References
  1. Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumors. Pathol int. 2006; 56:1-9.
  2. Nishida T, Blay JY, Hirota S, Kitagawa Y, Kang YK. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. Gastric Cancer. 2016; 19:3-14.
  3. Heinrich MC, Corless CL, Demetri GD, Blanke CD, Von Mehren M, Joensuu H et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J clin oncol. 2003; 21:4342-9.
  4. Heinrich MC, Maki RG, Corless CL, Antonescu CR, Harlow A, Griffith D, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J clin oncol. 2008; 26:5352.
  5. Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. The Lancet. 2007; 369:1731-41.
  6. Duensing S, Duensing A. Targeted therapies of gastrointestinal stromal tumors (GIST)”the next frontiers. Biochem pharmacol. 2010; 80:575-83.
  7. Cassier PA, Blay JY. Molecular response prediction in gastrointestinal stromal tumors. Targeted oncol. 2010; 5:29-37.
  8. Duensing A, Medeiros F, McConarty B, Joseph NE, Panigrahy D, Singer S, et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene. 2004; 23:3999.
  9. Niinuma T, Suzuki H, Sugai T. Molecular characterization and pathogenesis of gastrointestinal stromal tumor. Trans gastroenterol hepatol. 2018; 3.
  10. Shi SS, Wu N, He Y. EGFR gene mutation in gastrointestinal stromal tumours. Histopathol 2017; 71:553-61.
  11. Daniels M, Lurkin I, Pauli R, ErbstöíŸer E, Hildebrandt U, Hellwig K, et al. Spectrum of KIT/ PDGFRA/BRAF mutations and Phosphatidylinositol-3- Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST). Cancer Lett 2011; 312:43-54.
  12. Mei L, Smith SC, Faber AC, Trent J, Grossman SR, Stratakis CA, Boikos SA. Gastrointestinal stromal tumors: the GIST of precision medicine. Trends in Cancer. 2018; 4:74-91.
  13. Belinsky MG, Cai KQ, Zhou Y, Luo B, Pei J, Rink L, et al. Succinate dehydrogenase deficiency in a PDGFRA mutated GIST. BMC Cancer. 2017; 17:512.
  14. Heinrich MC, Corless CL, Blanke CD, Demetri GD, Joensuu H, Roberts PJ, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006; 24:4764-74.
  15. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin cancer res. 2005; 11:4182-90.
  16. Akahoshi K, Sumida Y, Matsui N, Oya M, Akinaga R, Kubokawa M, et al. Preoperative diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration. World J gastroentero: WJG. 2007; 13:2077.
  17. Yamaguchi U, Hasegawa T, Masuda T, Sekine S, Kawai A, Chuman H, et al. Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis. Virchows Archiv 2004; 445:142-50.
  18. Patil DT, Ma S, Konishi M, Carver PD, Pukay M, Beadling C, et al. Utility of BRAF V600E mutation-specific immunohistochemistry in detecting BRAF V600E-mutated gastrointestinal stromal tumors. Am J clin pathol. 2015; 144:782-9.
  19. Wang M, Xu J, Zhao W, Tu L, Qiu W, Wang C, et al. Prognostic value of mutational characteristics in gastrointestinal stromal tumors: a single-center experience in 275 cases. Medical Oncolo. 2014; 31:819.
  20. Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Sem in diag pathol 2006; 23:91-102.
  21. Martí­n-Broto J, Rubio L, Alemany R, López-Guerrero JA. Clinical implications of KIT and PDGFRA genotyping in GIST. Clin Trans Oncol. 2010; 12:670-6.
  22. Wozniak A, Rutkowski P, Piskorz A. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience. Ann Oncol 2012; 23:353-60.
  23. Debiec-Rychter M, Sciot R, Le Cesne A. EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian Gastrointestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006; 42:1093–1103.
  24. Wozniak A, Rutkowski P, Schöffski . Tumour genotype is an independent prognostic factor in primary gastrointestinal stromal tumours of gastric origin: a European multicenter analysis based on Contica GIST. Clin Cancer Res 2014; 20, 6105–6116.
  25. Heinrich MC, Owzar K, Corless CL. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumour: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol 2008; 26:5360–5367.
  26. Novelli M, Rossi S, Rodriguez"Justo M, Taniere P, Seddon B, Toffolatti L, et al. DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopatho. 2010; 57:259-70.
  27. Szucs Z, Thway K, Fisher C, Bulusu R, Constantinidou A, Benson C, et al. Molecular subtypes of gastrointestinal stromal tumors and their prognostic and therapeutic implications. Fut Oncol. 2017; 13:93-107.
  28. Gajiwala KS, Wu JC, Christensen J. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci U S A 2009; 106:1542-7.
  29. Martin-Broto J, Gutierrez A, Garcia-del-Muro X. Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study. Ann Oncol 2010; 21:1552-7.
  30. Steigen SE, Eide TJ, Wasag B. Mutations in gastrointestinal stromal tumors – a population-based study from Northern Norway. APMIS 2007; 115:289-98.
  31. Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, et al. Association of Exon 9 Mutations with Nongastric Primary Site and Aggressive Behavior. Clin Cancer Res 2003; 9:3329.
  32. Demetri GD, Von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Nat Comprehensive Cancer Net. 2010; 8:S-1.
  33. Heinrich MC, Corless CL, Duensing A. PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors. Science 2003; 299:708.
  34. Wozniak A, Rutkowski P, Schoffski P. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a European multicenter analysis based on ConticaGIST. Clin Cancer Res 2014; 20:6105-16.
  35. Lasota J, Dansonka-Mieszkowska A, Sobin LH. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 2004; 84:874-83.
  36. Sakurai S, Hasegawa T, Sakuma Y. Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: A subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene. Hum Pathol 2004; 35:1223-30.
  37. Kazemi E, Zargooshi J Kaboudi M, Heidari P, Kahrizi D, Mahaki B, Mohammadian Y, Khazaei H, Ahmed K. A genome-wide association study to identify candidate genes for erectile dysfunction. Brief Bioinform 2020; bbaa338, https://doi.org/10.1093/bib/bbaa338.
  38. Corless CL, Schroeder A, Griffith D. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005; 23:5357-64.
  39. 39. Lin J, Wang Y, Wei X, Kong S, Liu Z, Liu J, Zhang F, Lin S, Ji B, Zhou Z, Guo Z. Controllable antibacterial and bacterially anti-adhesive surface fabricated by a bio-inspired beetle-like macromolecule. Int J Biol Macromol 2020. Doi: 10.1016/j.ijbiomac.2020.04.207.
  40. 40. Liu G, Ren G, Zhao L, Cheng L, Wang C, Sun B. Antibacterial activity and mechanism of bifidocin A against Listeria monocytogenes. Food Control 2017; 73:854-61. Doi: 10.1016/j.foodcont.2016.09.036.
  41. 41. Jiang D, Chen FX, Zhou H, Lu YY, Tan H, Yu SJ, Yuan J, Liu H, Meng W, Jin ZB. Bioenergetic crosstalk between mesenchymal stem cells and various ocular cells through the intercellular trafficking of mitochondria. Theranostics 2020;10(16):7260. Doi: 10.7150/thno.46332.
  42. 42. Pan D, Xia XX, Zhou H, Jin SQ, Lu YY, Liu H, Gao ML, Jin ZB. COCO enhances the efficiency of photoreceptor precursor differentiation in early human embryonic stem cell-derived retinal organoids. Stem Cell Res Ther 2020; 11(1):1-2. Doi: 10.1186/s13287-020-01883-5.
  43. 43. Zhang J, Liu B. A review on the recent developments of sequence-based protein feature extraction methods. Curr Bioinform 2019; 14(3):190-9. Doi: 10.2174/1574893614666181212102749.
  44. 44. Xu L, Jiang S, Zou Q. An in silico approach to identification, categorization and prediction of nucleic acid binding proteins. bioRxiv. 2020. Doi: 10.1093/bib/ bbaa171.
  45. 45. Zhu S, Wang X, Zheng Z, Zhao XE, Bai Y, Liu H. Synchronous measuring of triptolide changes in rat brain and blood and its application to a comparative pharmacokinetic study in normal and Alzheimer's disease rats. Journal of Pharmaceutical and Biomedical Analysis. 2020; 113263. 10.1016/j.jpba.2020.113263.
  46. 46. Chen G, Li Y, Ren Z, Gu Y, Tang F, Mao J, Zhu J, Wang L, Li Y. Clinical Significance of MicroRNA-155-Regulated Autophagy and Apoptosis by Targeting Rictor/Fos in Gastric Cancer Progression. Nanosci Nanotechnol Lett 2020; 12(4):525-35.
  47. 47. Alkhudhayri AA, Wahab R, Siddiqui MA, Ahmad J. Selenium Nanoparticles Induce Cytotoxicity and Apoptosis in Human Breast Cancer (MCF-7) and Liver (HepG2) Cell Lines. Nanosci Nanotechnol Lett 2020; 12(3):324-30.
  48. 48. Su Q, Liu Y, Lv XW, Dai RX, Yang XH, Kong BH. LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis. Am J Physiol Heart Circ Physiol 2020; 318(2):H332-44. Doi: 10.1152/ajpheart.00444.2019.
  49. 49. Zhang T, Su H, Xing Y, Zhang J, Xu D. Protective Mechanism of Lipid-Lowering Ketone and Self-Assembled OA Chitosan Nanoparticles on Insulin Oxidative Stress. Induced by High Fat in BRL-3A Cells. Nanosci Nanotechnol Lett 2020; 12: 715–719.
  50. 50. Zhang D, Lu Z, Sun B. Highly Sensitive Gold Nanoparticle Polymerase Chain Reaction in the Detection of Anaplastic Lymphoma Kinase-Positive Gastric Cancer from a Biopsy Specimen. Nanosci Nanotechnol Lett 2020; 12(4):498-505.
  51. 51. Wang M, Hu M, Li Z, He L, Song Y, Jia Q, Zhang Z, Du M. Construction of Tb-MOF-on-Fe-MOF conjugate as a novel platform for ultrasensitive detection of carbohydrate antigen 125 and living cancer cells. Biosens Bioelectron 2019;142:111536. 10.1016/j.bios.2019.111536.
  52. 52. Jin Y, Zhu H, Zhu H, Jin F, Shi C, Yang L, Qian J, Zhang S. Fluorouracil Nanoliposomes Promote Apoptosis of Human Gastric Cancer Xenografts in Nude Mice. Nanosci. Nanotechnol. Lett 2020; 12: 690–695.
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