Yıl: 2022 Cilt: 32 Sayı: 1 Sayfa Aralığı: 16 - 22 Metin Dili: İngilizce DOI: 10.4999/uhod.225702 İndeks Tarihi: 02-06-2023

Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas

Öz:
Diffuse large B-cell lymphoma(DLBCL) is the prototype of aggressive lymphomas. The abnormalities such as translocation, deletion, duplication are stated to affect the progress and the prognosis of the disease. This study investigates the presence and impact on the prognosis of K-ras mutation and C-myc overexpression in patients with DLBCL. Twenty eight patients diagnosed with DLBCL and 29 healthy controls, whose diagnostic lymph node biopsy was reactive, were enrolled in this study. Paraffin blocks were analyzed for K-ras mutations and C-myc expressions. The effects of C-myc and K-ras on overall and disease-free survival were evaluated. Of the 28 patients, three (10.7%) K-ras mutations were detected. K-ras mutation (+) cases have an average survival time of 28 months, while those without the mutation were 49 months. The average duration of disease-free survival was 17.6 months in patients with K-ras mutation, while it has been identified as 45 months in patients without mutations (p= 0.072). C-myc overexpression in 17 patients(61%) was detected. Median overall survival was 33 months in male patients, while it was 65 months in female patients (p= 0.006). The median disease-free survival time was 23 months in male patients, although 64 months in female patients (p= 0.003). Complete remission rate was 30% in C-myc overexpression group, while 69% in remaining group with the cut-off 2.48 (p= 0.02). The presence of K-ras and C-myc overexpression in patients with DLBCL does not affect overall and disease-free survival. C-myc overexpression harms complete remission. Gender was found to be influential on the overall and disease-free survival; meanwhile, the female gender was a better prognosis.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major his- tologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol 16: 2780-2795, 1998.
  • 2. Corominas M, Perucho M, Newcomb EW, et al. Differential expression of the normal and mutated K-ras alleles in chemi- cally induced thymic lymphomas. Cancer Res 51: 5129- 5133, 1991.
  • 3. Ott G, Rosenwald A, Campo E. Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classifica - tion. Hematology Am Soc Hematol Educ Program 2013: 575-583, 2013.
  • 4. Facchini LM, Penn LZ. The molecular role of Myc in growth and transformation: recent discoveries lead to new insights. FASEB J 12: 633-651, 1998.
  • 5. Sakamuro D, Prendergast GC. New Myc-interacting proteins: a second Myc network emerges. Oncogene 18: 2942-2954, 1999.
  • 6. Klapproth K, Wirth T. Advances in the understanding of MYC- induced lymphomagenesis. Br J Haematol 149: 484-97, 2010.
  • 7. D’Angelo S, Liebermann D, Hoffman B. The c-myc apoptotic response is not intrinsic to blocking terminal myeloid differen- tiation. J Cell Physiol 216: 120-127, 2008.
  • 8. Tran PT, Fan AC, Bendapudi PK, et al. Combined Inactiva - tion of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PLoS One 3: e2125, 2008.
  • 9. Yeh E, Cunningham M, Arnold H, et al. A signalling pathway controlling c-Myc degradation that impacts oncogenic trans- formation of human cells. Nat Cell Biol 6: 308-318, 2004.
  • 10. Groves FD, Linet MS, Travis LB, et al. Cancer surveillance series: non-Hodgkin’s lymphoma incidence by histologic subtype in the United States from 1978 through 1995. J Natl Cancer Inst 92: 1240-1251, 2000.
  • 11. Tomita N, Kodama F, Motomura S, et al. Prognostic factors in diffuse large B-cell lymphoma treated by risk-adopted ther- apy. Intern Med 45: 247-252, 2006.
  • 12. Dave SS, Fu K, Wright GW, et al; Lymphoma/Leukemia Mo - lecular Profiling Project. Molecular diagnosis of Burkitt’s lym- phoma. N Engl J Med 354: 2431-2442, 2006.
  • 13. Schrader A, Bentink S, Spang R, et al. High Myc activity is an independent negative prognostic factor for diffuse large B cell lymphomas. Int J Cancer 131: E348-61, 2012.
  • 14. Magic Z, Novkovic T, Cikota B, et al. Genetic alterations in B-cell non-Hodgkin’s lymphoma. Vojnosanit Pregl 62: 87-96, 2005.
  • 15. Green TM, Nielsen O, de Stricker K, et al. High levels of nu - clear MYC protein predict the presence of MYC rearrange - ment in diffuse large B-cell lymphoma. Am J Surg Pathol 36: 612-619, 2012.
  • 16. Klapper W, Stoecklein H, Zeynalova S, et al; German High- Grade Non-Hodgkin’s Lymphoma Study Group. Structural aberrations affecting the MYC locus indicate a poor progno - sis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHN- HL). Leukemia 22: 2226-2229, 2008.
  • 17. Savage KJ, Johnson NA, Ben-Neriah S, et al. MYC gene rear- rangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemo- therapy. Blood 114: 3533-3537, 2009.
  • 18. Malkan UY, Gunes G, Yayar O, et al. Diffuse large B cell lym- phoma with extensive cutaneous relapse. Case Rep Med 2015: 137682, 2015.
  • 19. Akasaka T, Akasaka H, Ueda C, et al. Molecular and clinical features of non-Burkitt’s, diffuse large-cell lymphoma of B- cell type associated with the c-MYC/immunoglobulin heavy- chain fusion gene. J Clin Oncol 18: 510-518, 2000.
  • 20. Hummel M, Bentink S, Berger H, et al. A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profil - ing. N Engl J Med 354: 2419-2430, 2006.
  • 21. Nitsu N, Okamoto M, Miura I, et al. Clinical significance of 8q24/c-MYC translocation in diffuse large B-cell lymphoma. Cancer Sci 100: 233-237, 2009.
  • 22. Oberley MJ, Rajguru SA, Zhang C, et al. Immunohistochemi- cal evaluation of MYC expression in mantle cell lymphoma. Histopathology 63: 499-508, 2013.
APA Ertaş Ş, ÜNAL A, Akalın H, BARAN M, canöz ö, KONTAŞ O, OZKUL Y, Keklik M, Sivgin S, Eser B, Kaynar L, ÇETİN M (2022). Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. , 16 - 22. 10.4999/uhod.225702
Chicago Ertaş Şule Ketenci,ÜNAL ALİ,Akalın Hilal,BARAN MÜNEVVER,canöz özlem,KONTAŞ OLGUN,OZKUL YUSUF,Keklik Muzaffer,Sivgin Serdar,Eser Bülent,Kaynar Leylagul,ÇETİN Mustafa Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. (2022): 16 - 22. 10.4999/uhod.225702
MLA Ertaş Şule Ketenci,ÜNAL ALİ,Akalın Hilal,BARAN MÜNEVVER,canöz özlem,KONTAŞ OLGUN,OZKUL YUSUF,Keklik Muzaffer,Sivgin Serdar,Eser Bülent,Kaynar Leylagul,ÇETİN Mustafa Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. , 2022, ss.16 - 22. 10.4999/uhod.225702
AMA Ertaş Ş,ÜNAL A,Akalın H,BARAN M,canöz ö,KONTAŞ O,OZKUL Y,Keklik M,Sivgin S,Eser B,Kaynar L,ÇETİN M Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. . 2022; 16 - 22. 10.4999/uhod.225702
Vancouver Ertaş Ş,ÜNAL A,Akalın H,BARAN M,canöz ö,KONTAŞ O,OZKUL Y,Keklik M,Sivgin S,Eser B,Kaynar L,ÇETİN M Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. . 2022; 16 - 22. 10.4999/uhod.225702
IEEE Ertaş Ş,ÜNAL A,Akalın H,BARAN M,canöz ö,KONTAŞ O,OZKUL Y,Keklik M,Sivgin S,Eser B,Kaynar L,ÇETİN M "Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas." , ss.16 - 22, 2022. 10.4999/uhod.225702
ISNAD Ertaş, Şule Ketenci vd. "Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas". (2022), 16-22. https://doi.org/10.4999/uhod.225702
APA Ertaş Ş, ÜNAL A, Akalın H, BARAN M, canöz ö, KONTAŞ O, OZKUL Y, Keklik M, Sivgin S, Eser B, Kaynar L, ÇETİN M (2022). Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. Uluslararası Hematoloji-Onkoloji Dergisi, 32(1), 16 - 22. 10.4999/uhod.225702
Chicago Ertaş Şule Ketenci,ÜNAL ALİ,Akalın Hilal,BARAN MÜNEVVER,canöz özlem,KONTAŞ OLGUN,OZKUL YUSUF,Keklik Muzaffer,Sivgin Serdar,Eser Bülent,Kaynar Leylagul,ÇETİN Mustafa Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. Uluslararası Hematoloji-Onkoloji Dergisi 32, no.1 (2022): 16 - 22. 10.4999/uhod.225702
MLA Ertaş Şule Ketenci,ÜNAL ALİ,Akalın Hilal,BARAN MÜNEVVER,canöz özlem,KONTAŞ OLGUN,OZKUL YUSUF,Keklik Muzaffer,Sivgin Serdar,Eser Bülent,Kaynar Leylagul,ÇETİN Mustafa Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. Uluslararası Hematoloji-Onkoloji Dergisi, vol.32, no.1, 2022, ss.16 - 22. 10.4999/uhod.225702
AMA Ertaş Ş,ÜNAL A,Akalın H,BARAN M,canöz ö,KONTAŞ O,OZKUL Y,Keklik M,Sivgin S,Eser B,Kaynar L,ÇETİN M Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. Uluslararası Hematoloji-Onkoloji Dergisi. 2022; 32(1): 16 - 22. 10.4999/uhod.225702
Vancouver Ertaş Ş,ÜNAL A,Akalın H,BARAN M,canöz ö,KONTAŞ O,OZKUL Y,Keklik M,Sivgin S,Eser B,Kaynar L,ÇETİN M Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas. Uluslararası Hematoloji-Onkoloji Dergisi. 2022; 32(1): 16 - 22. 10.4999/uhod.225702
IEEE Ertaş Ş,ÜNAL A,Akalın H,BARAN M,canöz ö,KONTAŞ O,OZKUL Y,Keklik M,Sivgin S,Eser B,Kaynar L,ÇETİN M "Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas." Uluslararası Hematoloji-Onkoloji Dergisi, 32, ss.16 - 22, 2022. 10.4999/uhod.225702
ISNAD Ertaş, Şule Ketenci vd. "Impact of K-ras Mutation and C-myc Overexpression on the Prognosis of Diffuse Large B-Cell Lymphomas". Uluslararası Hematoloji-Onkoloji Dergisi 32/1 (2022), 16-22. https://doi.org/10.4999/uhod.225702