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Are PIK3CA Mutation and Amplification Associated with Clinicopathological Characteristics of Gastric Cancer?

  • Lee, Hyunsu (Department of Anatomy, Keimyung University College of Medicine) ;
  • Hwang, Il-Seon (Department of Pathology,Keimyung University College of Medicine) ;
  • Choi, In-Jang (Department of Anatomy, Keimyung University College of Medicine) ;
  • Kang, Yu-Na (Department of Pathology,Keimyung University College of Medicine) ;
  • Park, Keon-Uk (Division of Hematology/Oncology, Department of Internal Medicine, Keimyung University College of Medicine) ;
  • Lee, Jae-Ho (Department of Anatomy, Keimyung University College of Medicine)
  • Published : 2015.06.26

Abstract

Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non-cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC.

Keywords

References

  1. Bertelsen BI, Steine SJ, Sandvei R, Molven A, Laerum OD (2006). Molecular analysis of the PI3K-AKT pathway in uterine cervical neoplasia: frequent PIK3CA amplification and AKT phosphorylation. Int J Cancer, 118, 1877-83. https://doi.org/10.1002/ijc.21461
  2. Byun DS, Cho K, Ryu BK, et al (2003). Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma. Int J Cancer, 104, 318-27. https://doi.org/10.1002/ijc.10962
  3. Campbell IG, Russell SE, Choong DY, et al (2004). Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res, 64, 7678-81. https://doi.org/10.1158/0008-5472.CAN-04-2933
  4. Cancer Genome Atlas Research N (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 513, 202-9. https://doi.org/10.1038/nature13480
  5. Correa P (1992). Human gastric carcinogenesis: a multistep and multifactorial process-first American cancer society award lecture on cancer epidemiology and prevention. Cancer Res, 52, 6735-40.
  6. Correa P, Shiao YH (1994). Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res, 54, 1941-3.
  7. Garcia-Rostan G, Costa AM, Pereira-Castro I, et al (2005). Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res, 65, 10199-207. https://doi.org/10.1158/0008-5472.CAN-04-4259
  8. Gray JW, Collins C (2000). Genome changes and gene expression in human solid tumors. Carcinogenesis, 21, 443-52. https://doi.org/10.1093/carcin/21.3.443
  9. Kandula M, Chennaboina KK, Ammi Raju Y, Raju S (2013). Phosphatidylinositol 3-kinase (PI3KCA) oncogene mutation analysis and gene expression profiling in primary breast cancer patients. Asian Pac J Cancer Prev, 14, 5067-72. https://doi.org/10.7314/APJCP.2013.14.9.5067
  10. Kato S, Iida S, Higuchi T, et al (2007). PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int J Cancer, 121, 1771-8. https://doi.org/10.1002/ijc.22890
  11. Lee JW, Soung YH, Kim SY, et al (2005). PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene, 24, 1477-80. https://doi.org/10.1038/sj.onc.1208304
  12. Leung WK, Kim JJ, Kim JG, Graham DY, Sepulveda AR (2000). Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. Am J Pathol, 156, 537-43. https://doi.org/10.1016/S0002-9440(10)64758-X
  13. Lin Y, Jiang X, Shen Y, et al (2009). Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors. Endocr Relat Cancer, 16, 301-10.
  14. Ma YY, Wei SJ, Lin YC, et al (2000). PIK3CA as an oncogene in cervical cancer. Oncogene, 19, 2739-44. https://doi.org/10.1038/sj.onc.1203597
  15. Michl P, Downward J (2005). Mechanisms of disease: PI3K/ AKT signaling in gastrointestinal cancers. Z Gastroenterol, 43, 1133-9. https://doi.org/10.1055/s-2005-858638
  16. Ottini L, Falchetti M, Lupi R, et al (2006). Patterns of genomic instability in gastric cancer: clinical implications and perspectives. Ann Oncol, 17, 97-102. https://doi.org/10.1093/annonc/mdl245
  17. Qu JL, Qu XJ, Zhao MF, et al (2009). Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis, 41, 875-80. https://doi.org/10.1016/j.dld.2009.04.006
  18. Samuels Y, Wang Z, Bardelli A, et al (2004). High frequency of mutations of the PIK3CA gene in human cancers. Science, 304, 554. https://doi.org/10.1126/science.1096502
  19. Shayesteh L, Lu Y, Kuo WL, et al (1999). PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet, 21, 99-102. https://doi.org/10.1038/5042
  20. Shi J, Yao D, Liu W, et al (2012). Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer. BMC Cancer, 12, 50. https://doi.org/10.1186/1471-2407-12-50
  21. Velho S, Oliveira C, Ferreira A, et al (2005). The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer, 41, 1649-54. https://doi.org/10.1016/j.ejca.2005.04.022
  22. Wu G, Xing M, Mambo E, et al (2005). Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res, 7, 609-16. https://doi.org/10.1186/bcr1262
  23. Yamamoto H, Shigematsu H, Nomura M, et al (2008). PIK3CA mutations and copy number gains in human lung cancers. Cancer Res, 68, 6913-21. https://doi.org/10.1158/0008-5472.CAN-07-5084
  24. Yamamoto S, Tsuda H, Takano M, et al (2011). PIK3CA mutation is an early event in the development of endometriosisassociated ovarian clear cell adenocarcinoma. J Pathol, 225, 189-94. https://doi.org/10.1002/path.2940
  25. Yu HG, Ai YW, Yu LL, et al (2008). Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Int J Cancer, 122, 433-43. https://doi.org/10.1002/ijc.23049
  26. Zhang D, Wang Z, Luo Y, et al (2011). Analysis of DNA copy number aberrations by multiple ligation-dependent probe amplification on 50 intestinal type gastric cancers. J Surg Oncol, 103, 124-32. https://doi.org/10.1002/jso.21792

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