بررسی مولکولی جهشهای ژن CALR در کودکان مبتلا به سرطان خون بستری در بیمارستانهای شهر کرمان
محورهای موضوعی : سلولی ملکولیفرزانه پرناک 1 , بابک خیرخواه 2
1 - کارشناسی ارشد سلولی و مولکولی، دانشگاه آزاد اسلامی، واحد سیرجان، سیرجان، ایران
2 - استادیار، گروه میکروب‌شناسی، دانشگاه آزاد اسلامی، واحد کرمان، ایران
کلید واژه: سرطان خون, میلوفیبروز, جهش, ژن کالرتیکولین, ترومبوسیتمی,
چکیده مقاله :
هدف: جهش CALR به تازگی در نئوپلاسم‌های میلوپرولیفراتیو شناسایی شده است، اما اطلاعات اندکی در مورد بروز این جهش در ایران وجود دارد. مطالعه حاضر جهت بررسی مولکولی جهشهای ژن CALR در کودکان مبتلا به سرطان خون بستری در بیمارستانهای شهر کرمان انجام شد. مواد و روش‌ها: پژوهش حاضر از نوع مطالعه تجربی بوده و در آن جهش کالرتیکولین با روش نمونه‌گیری تصادفی ساده در 50 کودک بیمار یا در حال درمان مبتلا به بدخیمی‌های میلوپرولیفراتیو مورد ارزیابی قرار گرفت. برای تعیین جهش ابتدا DNA ژنومی از بافی کوت تهیه شده از خون محیطی استخراج شد و تعیین جهش به روش واکنش زنجیره‌ای پلیمراز با آلل اختصاصی انجام شد. سپس نمونه‌ها توالی‌یابی شدند. تعیین ارتباط نتایج حاصل با فاکتورهای دموگرافیک با استفاده از نرم‌افزار SPSS انجام شد. نتایج: 2/1% بیماران مبتلا به نئوپلاسم‌های میلوپرولیفراتیو مورد بررسی، دارای جهش CALR بودند. میزان جهش ژن CALR در گروه مطالعه قابل مقایسه با نتایج گزارش شده قبلی است. نتیجه‌گیری: براساس معیارهای سازمان بهداشت جهانی، از واکنش زنجیره‌ای پلیمراز با آلل اختصاصی می‌توان برای شناسایی این جهش در بیماران ایرانی مشکوک به نئوپلاسم‌های میلوپرولیفراتیو استفاده کرد.
Background: CALR mutation has recently been identified in myeloproliferative neoplasms, but little is known about the occurrence of this mutation in Iran. This study was performed to molecular study of CALR gene mutations in children with leukemia hospitalized in Kerman hospitals. Material and Methods:The present study was an experimental study. In this study, the mutation of calerticulin was evaluated by simple random sampling in 50 children or in the treatment of myeloproliferative malignancies. To determine the mutation, genomic DNA was first extracted from peripheral blood buffer and mutation was determined by polymerase chain reaction with specific allele. The samples were then sequenced. The results were correlated with demographic factors using SPSS software. Results: 1.2% of patients with myeloproliferative neoplasms had CALR mutation. The rate of CALR gene mutation in the study group is comparable with previous reported results. Conclusion: Therefore, according to WHO criteria, polymerase chain reaction with specific allele can be used to identify this mutation in Iranian patients with suspected myeloproliferative neoplasms.
Ranjbar-Zeidabadi H, Kheirkhah B. Molecular isolation of a human papilloma virus from blood serum in patients with leukemia in Kerman. Feyz. 2018; 22(4): 355-61.
Muñoz N, Bosch FX, De Sanjosé S, Herrero R,Castellsagué X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003; 348(6): 518-27.
World Cancer Report 2014. World Health Organization; 2014. p. Chapter 5.13. ISBN 9283204298.
Hutter JJ. Childhood leukemia. Pediatr Rev. 2010; 31(6): 234-41.
Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martínez-Trillos A, Casetti I, Colomer D, Pieri L, Pratcorona M, Rotunno G, Sant’Antonio E. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014; 124(7): 1062-9.
Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D. Somatic mutations of calreticulin in myeloproliferative neoplasms. N. Engl. J. Med. 2013; 369(25): 2379-90.
Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N. Engl. J. Med. 2013; 369(25): 2391-405.
Cui Y, Li B, Gale RP, Jiang Q, Xu Z, Qin T, Zhang P, Zhang Y, Xiao Z. CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia. J. Hematol. Oncol. 2014; 7(1): 77.
Imai M, Araki M, Komatsu N. Somatic mutations of calreticulin in myeloproliferative neoplasms. Int. J. Hematol. 2017; 105(6): 743-7.
Giona F, Teofili L, Capodimonti S, Laurino M, Martini M, Marzella D, Palumbo G, Diverio D, Foà R, Larocca LM. CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence. Blood. 2014; 123(23):
3677-9.
Li B, Xu J, Wang J, Gale RP, Xu Z, Cui Y, Yang L, Xing R, Ai X, Qin T, Zhang Y. Calreticulin mutations in Chinese with primary myelofibrosis. Haematologica. 2014;
99 (11): 1697-700.
Mansier O, Migeon M, Saint-Lézer A, James C, Verger E, Robin M, Socié G, Bidet A, Mahon FX, Cassinat B, Lippert E. Quantification of the mutant CALR Allelic Burden by Digital PCR: application to minimal residual disease evaluation after bone marrow transplantation. J. Mol. Diagn. 2016; 18(1): 68-74.
Pietra D, Rumi E, Ferretti VV, Di Buduo CA, Milanesi C, Cavalloni C, Sant'Antonio E, Abbonante V, Moccia F, Casetti IC, Bellini M. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms. Leukemia. 2016; 30(2): 431.
Tutt AN, van Oostrom CT, Ross GM, Van Steeg H, Ashworth A. Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation. EMBO reports. 2002; 3(3): 255-60.
Tamandani MK, Sobti RC, Shekari M, Mukesh M, Suri V. Expression and polimorphism of IFN-γ gene in patients with cervical cancer. Exp. Oncol. 2008; 30(3): 224-9.
Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, Ramoth LR, Rosen DG, Liu J, Hellstrom I, Smith D. Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin. Cancer Res. 2004; 10(10): 3291-300.
Pietrowski D, Thewes R, Sator M, Denschlag D, Keck C, Tempfer C. Uterine Leiomyoma is Associated with a Polymorphism in the Interleukin 1‐β Gene. Am. J. Reprod. Immunol. 2009; 62(2): 112-7.
Sull JW, Jee SH, Yi S, Lee JE, Park JS, Kim S, Ohrr H. The effect of methylenetetrahydrofolate reductase polymorphism C677T on cervical cancer in Korean women. Gynecol. Oncol. 2004; 95(3): 557-63.
Mei Q, Zhou D, Gao J, Shen S, Wu J, Guo L, Liang Z. The association between MTHFR 677C > T polymorphism and cervical cancer: evidence from a meta-analysis. BMC cancer. 2012; 12(1): 467.
Lambropoulos AF, Agorastos T, Foka ZJ, Chrisafi S, Constantinidis TC, Bontis J, Kotsis A. Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia. Cancer letters. 2003; 191(2): 187-91.
Zoodsma M, Nolte IM, Schipper M, Oosterom E, Van Der Steege G, de Vries EG, Te Meerman GJ, van der Zee AG. Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study. J. Med. Genet. 2005; 42(8): e49.
Shekari M, Sobti RC, Tamandani DM, Suri V. Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population. Arch. Gynecol. Obstet. 2008; 278(6): 517-24.
Wu S, Lu S, Tao H, Zhang L, Lin W, Shang H, Xie J. Correlation of polymorphism of
IL-8 and MMP-7 with occurrence and lymph node metastasis of early stage cervical cancer. J. Huazhong Univ. Sci. Technol., Med. Sci. 2011; 31(1): 114-9.
Ranjbar-Zeidabadi H, Kheirkhah B. Molecular isolation of a human papilloma virus from blood serum in patients with leukemia in Kerman. Feyz. 2018; 22(4): 355-61.
Muñoz N, Bosch FX, De Sanjosé S, Herrero R,Castellsagué X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003; 348(6): 518-27.
World Cancer Report 2014. World Health Organization; 2014. p. Chapter 5.13. ISBN 9283204298.
Hutter JJ. Childhood leukemia. Pediatr Rev. 2010; 31(6): 234-41.
Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martínez-Trillos A, Casetti I, Colomer D, Pieri L, Pratcorona M, Rotunno G, Sant’Antonio E. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014; 124(7): 1062-9.
Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D. Somatic mutations of calreticulin in myeloproliferative neoplasms. N. Engl. J. Med. 2013; 369(25): 2379-90.
Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N. Engl. J. Med. 2013; 369(25): 2391-405.
Cui Y, Li B, Gale RP, Jiang Q, Xu Z, Qin T, Zhang P, Zhang Y, Xiao Z. CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia. J. Hematol. Oncol. 2014; 7(1): 77.
Imai M, Araki M, Komatsu N. Somatic mutations of calreticulin in myeloproliferative neoplasms. Int. J. Hematol. 2017; 105(6): 743-7.
Giona F, Teofili L, Capodimonti S, Laurino M, Martini M, Marzella D, Palumbo G, Diverio D, Foà R, Larocca LM. CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence. Blood. 2014; 123(23):
3677-9.
Li B, Xu J, Wang J, Gale RP, Xu Z, Cui Y, Yang L, Xing R, Ai X, Qin T, Zhang Y. Calreticulin mutations in Chinese with primary myelofibrosis. Haematologica. 2014;
99 (11): 1697-700.
Mansier O, Migeon M, Saint-Lézer A, James C, Verger E, Robin M, Socié G, Bidet A, Mahon FX, Cassinat B, Lippert E. Quantification of the mutant CALR Allelic Burden by Digital PCR: application to minimal residual disease evaluation after bone marrow transplantation. J. Mol. Diagn. 2016; 18(1): 68-74.
Pietra D, Rumi E, Ferretti VV, Di Buduo CA, Milanesi C, Cavalloni C, Sant'Antonio E, Abbonante V, Moccia F, Casetti IC, Bellini M. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms. Leukemia. 2016; 30(2): 431.
Tutt AN, van Oostrom CT, Ross GM, Van Steeg H, Ashworth A. Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation. EMBO reports. 2002; 3(3): 255-60.
Tamandani MK, Sobti RC, Shekari M, Mukesh M, Suri V. Expression and polimorphism of IFN-γ gene in patients with cervical cancer. Exp. Oncol. 2008; 30(3): 224-9.
Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, Ramoth LR, Rosen DG, Liu J, Hellstrom I, Smith D. Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin. Cancer Res. 2004; 10(10): 3291-300.
Pietrowski D, Thewes R, Sator M, Denschlag D, Keck C, Tempfer C. Uterine Leiomyoma is Associated with a Polymorphism in the Interleukin 1‐β Gene. Am. J. Reprod. Immunol. 2009; 62(2): 112-7.
Sull JW, Jee SH, Yi S, Lee JE, Park JS, Kim S, Ohrr H. The effect of methylenetetrahydrofolate reductase polymorphism C677T on cervical cancer in Korean women. Gynecol. Oncol. 2004; 95(3): 557-63.
Mei Q, Zhou D, Gao J, Shen S, Wu J, Guo L, Liang Z. The association between MTHFR 677C > T polymorphism and cervical cancer: evidence from a meta-analysis. BMC cancer. 2012; 12(1): 467.
Lambropoulos AF, Agorastos T, Foka ZJ, Chrisafi S, Constantinidis TC, Bontis J, Kotsis A. Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia. Cancer letters. 2003; 191(2): 187-91.
Zoodsma M, Nolte IM, Schipper M, Oosterom E, Van Der Steege G, de Vries EG, Te Meerman GJ, van der Zee AG. Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study. J. Med. Genet. 2005; 42(8): e49.
Shekari M, Sobti RC, Tamandani DM, Suri V. Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population. Arch. Gynecol. Obstet. 2008; 278(6): 517-24.
Wu S, Lu S, Tao H, Zhang L, Lin W, Shang H, Xie J. Correlation of polymorphism of
IL-8 and MMP-7 with occurrence and lymph node metastasis of early stage cervical cancer. J. Huazhong Univ. Sci. Technol., Med. Sci. 2011; 31(1): 114-9.