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Lack of CHEK2 Gene Mutations in Differentiated Thyroid Carcinoma Patients using High Resolution Melting Analysis

  • Published : 2014.06.30

Abstract

Recently, mutations in the genes involved in cell cycle control, including CHEK2, are being considered as etiological factors in different kinds of cancers. The CHEK2 protein plays an important role in protecting damaged DNA from entering mitosis. In this study the potential effects of two common mutations $IVS2+1G{\rightarrow}A$ and Ile157Thr of CHEK2 gene in differentiated thyroid carcinoma (DTC) were evaluated. A total of 100 patients admitted to the Research Institute for Nuclear Medicine were diagnosed with DTC based on pathology reports of surgery samples. An additional 100 people were selected as a control group with no cancer history. PCR-HRM (high resolution melting) analysis was performed to deal with each of mutations in all case and control samples separately. During the analysis of $IVS2+1G{\rightarrow}A$ and Ile157Thr mutations of CHEK2 gene in the case and control groups, all the samples were identified as wild homozygote type. The finding suggests that $IVS2+1G{\rightarrow}A$ and Ile157Thr mutations of CHEK2 gene do not constitute a risk factor for DTC in the Iranian population. However, further studies with larger population are required to confirm the outcome.

Keywords

References

  1. Ahn JY, Li X, Davis HL, Canman CE (2002). Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J Biol Chem, 277, 19389-95. https://doi.org/10.1074/jbc.M200822200
  2. Bayram S, Topaktas M, Akkiz H, Bekar A, Akgollu E (2012). CHEK2 1100delC, IVS2+1G>A and I157T mutations are not present in colorectal cancer cases from Turkish population. Cancer Epidemiol, 36, 453-7. https://doi.org/10.1016/j.canep.2012.03.008
  3. Chehab NH, Malikzay A, Appel M, Halazonetis TD (2000). Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev, 14, 278-88.
  4. Cybulski C, Gorski B, Huzarski T, et al (2004). CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet, 75, 1131-5. https://doi.org/10.1086/426403
  5. Debniak T, Scott RJ, Gorski B, et al (2008). Common variants of DNA repair genes and malignant melanoma. Eur J Cancer, 44, 110-4. https://doi.org/10.1016/j.ejca.2007.10.006
  6. Hundahl SA, Fleming ID, Fremgen AM , Menck HR (1998). A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments]. Cancer, 83, 2638-48. https://doi.org/10.1002/(SICI)1097-0142(19981215)83:12<2638::AID-CNCR31>3.0.CO;2-1
  7. Kleibl Z, Havranek O, Novotny J, et al (2008). Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations. Breast Cancer Res Treat, 112, 159-64. https://doi.org/10.1007/s10549-007-9838-7
  8. Kleibl Z, Havranek O, Hlavata I, et al (2009). The CHEK2 gene I157T mutation and other alterations in its proximity increase the risk of sporadic colorectal cancer in the Czech population. Eur J Cancer, 45, 618-24. https://doi.org/10.1016/j.ejca.2008.09.022
  9. Khayamzadeh M, Tadayon N, Salmanian R, et al (2011). Survival of thyroid cancer and social determinants in Iran, 2001-2005. Asian Pac J Cancer Prev, 12, 95-8.
  10. Liang J, Wang Y, Miao L, et al (2000). Nonsyndromic cleft lip with or without cleft palate in Chinese population: analysis of 3766 cases. Hua Xi Yi Ke Da Xue Xue Bao, 31, 408-10 (in Chinese).
  11. Liu C1, Wang Y, Wang QS, Wang YJ (2012). The CHEK2 I157T variant and breast cancer susceptibility: a systematic review and meta-analysis. Asian Pac J Cancer Prev, 13, 1355-6 https://doi.org/10.7314/APJCP.2012.13.4.1355
  12. Liu C, Wang QS, Wang YJ (2012).The CHEK2 I157T variant and colorectal cancer susceptibility: a systematic review and meta-analysis. Asian Pac J Cancer Prev, 13, 2051-5. https://doi.org/10.7314/APJCP.2012.13.5.2051
  13. Miller SA, Dykes DD ,Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16, 1215. https://doi.org/10.1093/nar/16.3.1215
  14. Szymanska-Pasternak J, Szymanska A, Medrek K, et al (2006). CHEK2 variants predispose to benign, borderline and lowgrade invasive ovarian tumors. Gynecol Oncol, 102, 429-31. https://doi.org/10.1016/j.ygyno.2006.05.040