Mutation Analysis of TP53 Tumor Suppressor Gene in Colorectal Cancer in Patients from Iran (Kerman Province)

Authors

Department of Biotechnology, Research Institute for Environmental Sciences, International Centre for Science, High Technology and Environmental Sciences, Kerman, Iran

Abstract

Objective(s)
P53 is an important tumor suppressor, which is mutated in later stages of many cancers and leads to resistance to chemotherapy. The aim of this study was to reveal mutations of TP53 in colorectal cancer in Kerman province.
Materials and Methods
A total of Forty-three colon cancer specimens as paraffin block or fresh tissues, which passed stage IIIA, were selected. Three exons 5, 7 and 8 of P53 were amplified by PCR technique and sequenced directly.
Results
The results showed two deletions at codon 140 and 142 in one tumor sample. GAT→AAT mutation at codon 184, and CGG→TGG mutation at codon 248 were seen in some tumor samples. Some mutations were also observed in middle of intron 7 in some tumor or normal tissues.
Conclusion
Some of those patients with mutation in P53 gene had metastasis in other organs. Therefore, genetic test before chemotherapy is helpful for successful treatment.

Keywords


1. Parkin D, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999; 80:827-841.
2. UK CR. Bowel Cancer incidence statistics. Available at.http://info.cancerresearchuk.org/cancerstats/types/bowel/incidence/
3. Wang Y, Kringen P, Kristensen G, Holm R, Baekelandt M, Olivier M, et al. Effect of the codon 72 polymorphism (c215G>C  pArg72Pro) in combination with somatic sequence variants in the TP53 gene on survival in patients with advanced ovarian carcinoma. Hum Mutat 2004; 24:21-34.
4. Compton C, Greene F. The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 2004; 54:295-308.
5. Wilke H-J, Van Cutsem E. Current treatments and future perspectives in colorectal and gastric cancer. Ann Oncol 2003; 14:ii49–ii55.
6. Boyle P, J L. ABC of colorectal cancer: Epidemiology. BMJ  2000; 321:805-808.
7. Kemp Z, Thirlwell C, Sieber O, Silver A, Tomlinson I. An update on the genetics of colorectal cancer. Hum Mol Genet 2004; 13:R177–R85.
8. Webley K, Shorthouse A, Royds J. Effect of mutation and conformation on the function of P53 in colorectal cancer. J Pathol  2000; 191:361-367
9. Calistri D, Rengucci C, Seymour I, Lattuneddu A, Polifemo A, Monti F, et al. Mutation analysis of P53, K-ras, and BRAF genes in colorectal cancer progression. J Cell Physiol 2005; 204:484-488.
10. Morgunkova A. The P53 gene family: control of cell proliferation and developmental programs. Biochemistry (Mosc) 2005; 70:955-971.
11. Vousden KH, Lane DP. P53 in health and disease. Natr Rev Mol Cell Biol  2007; 8:275-283.
12. Hjortsberg L, Rubio-Nevado J, Hamroun D, Claustre M, Béroud C, Soussi T. The P53 Mutation Hand Book 2.02008.
13. Munro A, Lain S, Lane D. P53 abnormalities and outcomes in colorectal cancer: a systematic review. Br J Cancer  2005; 92:434–44.
14. Iacopetta B. TP53 mutation in colorectal cancer. Hum Mutat  2003; 21:271-276.
15. Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst  2001; 93:583-596.
16. Lyall MS, Dundas SR, Curran S, Murray  GI. Profiling Markers of Prognosis in Colorectal Cancer. Clin Cancer Res  2006; 12:1184-1191.
17. Iacopetta B, Russo A, Bazan V, Dardanoni G, Gebbia N. Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study. Ann Oncol 2006; doi:10.1093/annonc/mdl035.
18. Lam A, Ong K, Ho Y. hTERT expression in colorectal adenocarcinoma: correlations with p21, P53 expressions and clinicopathological features. Int J Colorectal Dis  2008; 23:587-594.
19. Giménez-Bonafé P, Tortosa A, Pérez-Tomás R. Overcoming drug resistance by enhancing apoptosis of tumor cells. Curr Cancer Drug Targets  2009; 9:320-340.
20. Benhattar J, Cerottini JP, Saraga E, Metthez G, Givel JC. P53 mutations as a possible predictor of response to chemotherapy in metastatic colorectal carcinomas. Int J Cancer 1996; 69:190-192.
21. Viktorsson K, De Petris L, Lewensohn R. The role of P53 in treatment responses of lung cancer. Biochem Biophys Res Commun 2005; 331:868-880.
22. Yu JL, Rak JW, L CB, Hicklin DJ, Kerbel RS. Effect of P53 status on tumor response to antiangiogenic therapy. Science 2002; 295:1526-1528.
23. Boyer J, McLean E, Aroori S, Wilson P, McCulla A, Carey P, et al. Characterization of P53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan. Clin Cancer Res 2004; 10:2158-2167.
24.Reles A, Wen W, Schmider A, Gee C, Runnebaum I, Kilian U, et al. Correlation of P53 Mutations with Resistance to Platinum-based Chemotherapy and Shortened Survival in Ovarian Cancer. Clin Cancer Res  2001; 7:2984-2997
25. Weekes J, Lam A, Sebesan S, Ho Y. Irinotecan therapy and molecular targets in colorectal cancer: a systemic review. World J Gastroenterol  2009; 15:3597-3602.
26. Wilke H, Van Cutsem E. Current treatments and future perspectives in colorectal and gastric cancer. Ann Oncol 2003; 14:ii49-ii55.
27. Mahdavinia M, Bishehsari F, Verginelli F, Cumashi A, Lattanzio R, Sotoudeh M, et al. P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations. . J Cell Physiol 2008; 216:543-550.
28. Coombs NJ, Gough A, Primrose JN. Optimization of DNA and RNA extraction from archival formalin-fixed tissue. Nucleic Acids Res  1999; 27:e12.
29. Srinivasan M, Sedmak D, Jewell S. Effect of fixatives and Tissue processing on the content and integrity of nucleic acids. Am J Pathol  2002; 161.
30. Coura R, Prolla JC, Meurer L, Ashton-Prolla P. An alternative protocol for DNA extraction from formalin fixed and paraffin wax embedded tissue. J Clin Pathol 2005; 58:894–895.
31. Lohrasbi Nejad A, Yaghoobi M, Nazem H. Optimization of DNA extraction from paraffin embedded tissues By a combinatory procedure I. J Biol  2010; 23:132-140.
32. Tseng J, Rodriguez L, Ro J, Liu D, Hong W, Mao L. Gender differences in P53 mutational status in small cell lung cancer. Cancer Res 1999; 59:5666-5670
33. Baumbusch L, Myhre S, Langerod A, Bergamaschi A, Geisler S, Lonning P, et al. Expression of full-length P53 and its isoform Delta P53 in breast carcinomas in relation to mutation status and clinical parameters. Mol Cancer  2006; 5:47.
34. Angelopoulou K, Levesque M, Katsaros D, Shipman R, Diamandis E. Exon 5 of the P53 gene is a target for deletions in ovarian cancer.  Clin Chem 1998; 44:72-27
35. Alsner J,Yilmaz M, Guldberg P,Hansen L, Overgaard J. Heterogeneity in the clinical phenotype of TP53 mutations in breast cancer patients. Clin Cancer Res  2000; 6:3923-3931
36. Pineau P, Marchio A, Battiston C, Cordina E, Russo A, Terris B, et al. Chromosome instability in human hepatocellular carcinoma depends on P53 status and aflatoxin exposure. Mutat Res 2008; 653.
37. Xinarianos G, Liloglou T, Prime W, Sourvinos G, Karachristos A, Gosney J, et al. P53 status correlates with the differential expression of the DNA mismatch repair protein MSH2 in non-small cell lung carcinoma. Int J Cancer  2002; 101:248-252.
38. Ambs S, Bennett W, Merriam W, Ogunfusika M, Oser S, Harrington A, et al. Relationship between P53 mutations and inducible nitric oxide synthase expression in human colorectal cancer. J Natl Cancer Inst 1999; 91:86-88.