Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Promyelocytic Leukemia (PML) Gene Mutations may not Contribute to Gastric Adenocarcinoma Development

  • Imani-Saber, Zeinab (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences) ;
  • Yousefi-Razin, Ehsan (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences) ;
  • Javaheri, Mona (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences) ;
  • Mirfakhraie, Reza (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences) ;
  • Motalleb, Gholamreza (Department of Biology, Faculty of Science, University of Zabol) ;
  • Ghafouri-Fard, Soudeh (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences)
  • Published : 2015.04.29
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Abstract

Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.

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References

  1. Babaei M, Pourfarzi F, Yazdanbod A, et al (2010). Gastric cancer in Ardabil, Iran--a review and update on cancer registry data. Asian Pac J Cancer Prev, 11, 595-9.
  2. Bahram B, Seyed N, Moslemi E, et al (2009). Insulin receptor gene mutations in Iranian patients with type II diabetes mellitus. Iranian biomedical journal, 13, 161-8.
  3. Campos FI, Koriyama C, Akiba S, et al (2006). Environmental factors related to gastric cancer associated with Epstein-Barr virus in Colombia. Asian Pac J Cancer Prev, 7, 633-7.
  4. Guo A, Salomoni P, Luo J, et al (2000). The function of PML in p53-dependent apoptosis. Nat Cell Biol, 2, 730-6. https://doi.org/10.1038/35036365
  5. Gurrieri C, Capodieci P, Bernardi R, et al (2004a). Loss of the tumor suppressor PML in human cancers of multiple histologic origins. J Natl Cancer Inst, 96, 269-79. https://doi.org/10.1093/jnci/djh043
  6. Gurrieri C, Nafa K, Merghoub T, et al (2004b). Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia. Blood, 103, 2358-62. https://doi.org/10.1182/blood-2003-07-2200
  7. Haidari M, Nikbakht MR, Pasdar Y, et al (2012). Trend analysis of gastric cancer incidence in Iran and its six geographical areas during 2000-2005. Asian Pac J Cancer Prev, 13, 3335-41. https://doi.org/10.7314/APJCP.2012.13.7.3335
  8. Imani-Saber Z, Ghafouri-Fard S (2014). Promyelocytic leukemia gene functions and roles in tumorigenesis. Asian Pac J Cancer Prev, 15.
  9. Karami N, Talebkhan Y, Saberi S, et al (2013). Seroreactivity to Helicobacter pylori antigens as a risk indicator of gastric cancer. Asian Pac J Cancer Prev, 14, 1813-7. https://doi.org/10.7314/APJCP.2013.14.3.1813
  10. Kyrlagkitsis I, Karamanolis D (2003). Genes and gastric cancer. Hepato-gastroenterology, 51, 320-7.
  11. Lee HE, Jee CD, Kim MA, et al (2007). Loss of promyelocytic leukemia protein in human gastric cancers. Cancer letters, 247, 103-9. https://doi.org/10.1016/j.canlet.2006.03.034
  12. Nagini S (2012). Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol, 4, 156-69. https://doi.org/10.4251/wjgo.v4.i7.156
  13. Namikawa T, Hanazaki K (2010). Mucin phenotype of gastric cancer and clinicopathology of gastric-type differentiated adenocarcinoma. World J Gastroenterol, 16, 4634-9. https://doi.org/10.3748/wjg.v16.i37.4634
  14. Pearson M, Carbone R, Sebastiani C, et al (2000). PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature, 406, 207-10. https://doi.org/10.1038/35018127
  15. Ravnik-Glavac M, Glavac D, Dean M (1994). Sensitivity of single-strand conformation polymorphism and heteroduplex method for mutation detection in the cystic fibrosis gene. Hum Mol Genet, 3, 801-7. https://doi.org/10.1093/hmg/3.5.801
  16. Salomoni P, Pandolfi PP (2002). The role of PML in tumor suppression. Cell, 108, 165-70. https://doi.org/10.1016/S0092-8674(02)00626-8
  17. Sheffield VC, Beck JS, Kwitek AE, et al (1993). The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics, 16, 325-32. https://doi.org/10.1006/geno.1993.1193
  18. Sivachandran N, Dawson CW, Young LS, et al (2012). Contributions of the Epstein-Barr virus EBNA1 protein to gastric carcinoma. J Virol, 86, 60-8. https://doi.org/10.1128/JVI.05623-11
  19. Takada K (2000). Epstein-Barr virus and gastric carcinoma. Mol Pathol, 53, 255-61. https://doi.org/10.1136/mp.53.5.255
  20. Wang LT, Smith A, Iacopetta B, et al (1996). Nested PCR-SSCP assay for the detection of p53 mutations in paraffin wax embedded bone tumours: improvement of sensitivity and fidelity. Clin Mol Pathol, 49, 176-8. https://doi.org/10.1136/jcp.49.2.176
  21. Wroblewski LE, Peek RM, Jr., Wilson KT (2010). Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev, 23, 713-39. https://doi.org/10.1128/CMR.00011-10
  22. Zhong S, Salomoni P, Pandolfi PP (2000). The transcriptional https://doi.org/10.1038/35010583