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TP53 Codon 72 Polymorphism and Risk of Acute Leukemia

  • Dunna, Nageswara Rao (School of Chemical & Biotechnology, SASTRA University) ;
  • Vure, Sugunakar (Department of Genetics, Osmania University) ;
  • Sailaja, K. (Department of Genetics, Osmania University) ;
  • Surekha, D. (Department of Genetics, Osmania University) ;
  • Raghunadharao, D. (Department of Medical Oncology, Nizams Institute of Medical Sciences) ;
  • Rajappa, Senthil (Department of Medical Oncology, Nizams Institute of Medical Sciences) ;
  • Vishnupriya, S. (Department of Genetics, Osmania University)
  • Published : 2012.01.31

Abstract

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (${\chi}^2$- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

Keywords

References

  1. Beckman G, Birgander Z, Sjalander A, et al (1994). Is p53 polymorphism maintained by natural selection? Hum Hered, 44, 266-70. https://doi.org/10.1159/000154228
  2. BenYehuda D, Krichevsky S, Caspi O, et al (1996). Microsatellite instability and p53 mutation in therapy-related leukemia suggest mutator photypes, Blood, 88, 3022-6.
  3. Bergamaschi D, Samuels Y, Sullivan A, et al (2006). iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nat Genet, 38, 1133-41. https://doi.org/10.1038/ng1879
  4. Crook T, Ludwing RL, Marston N, et al (1996). Sensitivity of p53 lysine mutants to ubiqitin-directed degradation targeted by human papillomavirus. Virology, 217, 285-92. https://doi.org/10.1006/viro.1996.0115
  5. Donehower LA, Bardley A (1993). The tumor suppressor p53. Biochimica et Biophysica Act, 1155, 181-205.
  6. Dumont Patrick, J. I-Ju Leu , Anthony C, et al (2003). The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nature Genetics, 33, 357-65. https://doi.org/10.1038/ng1093
  7. Fenaux P, Preudhomme C, Quiquandon I, et al (1992). Mutation of the p53 gene in acute myeloid leukemia. Br J Haematol, 80, 178-83. https://doi.org/10.1111/j.1365-2141.1992.tb08897.x
  8. Fenaux P, Preudhomme C, Quiquandon I, et al (1991). TP53 gene mutation in acute myeloid leukemia with 17p monosomy. Blood, 78, 1652-7.
  9. Gottlieb E, Moshe O (1998). P53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity of p53. EMBO J, 17, 3587-96. https://doi.org/10.1093/emboj/17.13.3587
  10. Greenblatt MS, Bennett Wp, Hollstein M, et al (1994). Mutation in the p53 tumor suppressor gene.clues to cancer etiology and molecular pathogenesis. Cancer Res, 54, 4855-78.
  11. Hollstein M, Shomer B, Greenblatt M, et al (1996) . Datebase of p53 gene somatic mutation in human tumors and cell lines. Nul. Acids Res, 24, 141-6. https://doi.org/10.1093/nar/24.1.141
  12. Hu G, Zhang W, Deisseroth AB (1992). P53 gene mutations myelogenous leukaemia. Br J Haematol, 81, 489-94. https://doi.org/10.1111/j.1365-2141.1992.tb02979.x
  13. Ko LJ, Prives C (1996). p53: puzzle and paradigm. Genes Dev, 10, 1054-72. https://doi.org/10.1101/gad.10.9.1054
  14. Lahari D, Nuremberg J (1991). A rapid non-enzymatic method for the preparation of HMW DNA from blood RFLP studies. Nucleic Acid Research, 19, 5444-?. https://doi.org/10.1093/nar/19.19.5444
  15. Lane DP, Benchimol S (1990). p53: oncogene or anti-oncogene? Genes & Development, 4, 1-8. https://doi.org/10.1101/gad.4.1.1
  16. Martin MC, Jost CA, Brooks LA, et al (2000). A common polymorphism acts as an intragenic modifier of mutant p53 behavior. Nat Genet, 25, 47-54. https://doi.org/10.1038/75586
  17. Nigro JM, Baker SJ, Preisinger AC Jessup JM, et al (1989). Mutation in the p53 gene occur in diverse human tumour types. Nature, 342, 705-8. https://doi.org/10.1038/342705a0
  18. Nurbuyru, Hatice Tigli, Nejat Dalay (2003). p53 codon 72 polymorphism in breast cancer. Oncology Reports, 10, 711-4.
  19. Olivier M, Eeles R, Hollstein M, et al. (2002) Hum Mutat, 19, 607-14. https://doi.org/10.1002/humu.10081
  20. Preudhomme C, Fenaux P (1997). the clinical significance of mutation of the p53 tumor suppressor gene in haematological malignances. Br J Haematol, 98, 502.
  21. Prives C (1998). Signaling to p53: Breaking the MDM2-p53 circuit. Cell, 95, 5-8. https://doi.org/10.1016/S0092-8674(00)81774-2
  22. Siddique MM, Balram C, Fiszer-Maliszewska L, et al (2005). Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development. Cancer Epidemiol Biomarkers Prev, 14, 2245-52. https://doi.org/10.1158/1055-9965.EPI-05-0153
  23. Slingerland JM, Minden MD. Benchimol S (1991). Mutation of the p53 gene in human acute myelogenous Leukemia. Blood, 77, 1500-7.
  24. Sugimoto K, Toyoshima H, et al (1992). Frequent mutation in the p53 gene in human myloid leukemia cell lines. Blood, 79, 2378-883.
  25. Teodoro J.G, Sara K, Evans, et al (2007). Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome: J Mol Med, 85, 1175-86. https://doi.org/10.1007/s00109-007-0221-2
  26. Thomas M, Kalita A, Labrecque S, et al (1999). Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol, 19, 1092-100. https://doi.org/10.1128/MCB.19.2.1092
  27. Wang YC, Lee HS, Chen Sk, et al (1999). Prognostic significance of p53 in growth control and neoplasia. Eur J Cancer, 35, 226-30. https://doi.org/10.1016/S0959-8049(98)00369-4
  28. Weston A, Ling-Cawley HM, Caporaso NE, et al (1994). Determination of the allelic frequencies of an L-myc and a p53polymorphism in human lung cancer. Carcinogenesis, 15, 583-7. https://doi.org/10.1093/carcin/15.4.583

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