PI3K pathway gene polymorphismin breast cancer tissues proliferation with synergistic effect of EBV- LMP1 oncogene activity among breastcancer patients in Basrah, southern of Iraq
Main Article Content
Keywords
PI3K,Invasive ductal carcinoma, Breast cancer
Abstract
PI3K is an intracellular heterodimer of two subunits regulater and catalytic one, induces many signalling pathways after activation. Specific primers used to detect PI3K in breast tissues of 186 patients with 84 benign of fibroadenoma and 72 invasive ductal carcinoma. conventional PCR detects that 97% of PI3K genome identity with standard strain and from 42 samples send to sequencing , there
were (38.1%) ofPI3KCA samples were mutated, when 15 (93.75%) of them in malignant and just one (6.25%) was benign. PI3KCA mutation increased with the advancing grades of malignant tissue especially in grade III, and the variation increased directly with the age. It has been noticed that PI3K pathways mutation and EBV-LMP1 have a directly effect on tumor progression . PIK3CA
mutationswere positively corelated with EBV-positive invasive ductal carcinoma and also associatedwith the mutation loci where those in exon 9 (ΔE542K), and exon 20 (ΔH1047R)are frequently detected and associated with greater PIK3CA mutations
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24. Samuels, Y.; Diaz, L.A.; Schmidt-Kittler, O.; Cummins, J.M.; Delong, L.; Cheong, I.; Rago, C.; Huso, D.L.; Lengauer, C.; Kinzler, K.W.; et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 2005,7, 561–573.
25. Huayu Hu, Junyong Zhu, Yuting Zhong, Rui Geng, Yashuang Ji, Qingyu Guan, et al . PIK3CA mutation confers resistance to chemotherapy in triple-negative breast cancer by inhibiting apoptosis and activating the PI3K/AKT/mTOR signaling pathway. Ann Transl Med 2021;9(5):410 | http://dx.doi.org/10.21037/atm-21-698
26. Karakas, B.; Bachman, K.E.; Park, B.H. Mutation of the PIK3CA oncogene in human cancers. Br. J. Cancer 2006, 94, 455–459.
27. Rand, A.; Yardena, S. PIK3CA in cancer: The past 30 years. Semin. Cancer. Biol. 2019, 59, 36–49
28. Paola Fuso 1,* , Margherita Muratore 1, Tatiana D’Angelo 2, Ida Paris 1 , Luisa Carbognin 1,Giordana Tiberi 1,et al.PI3K Inhibitors in
Advanced Breast Cancer: The Past, The Present,New Challenges and Future Perspectives.Cancers 2022, 14, 2161 :1-21
29. Bizhani F, Hashemi M, Danesh H, Nouralizadeh A, Narouie B,Bahari G, et al. Association between single nucleotidepolymorphisms in the PI3K/AKT/mTOR pathway and bladdercancer risk in a sample of Iranian population. EXCLI J2018;17:3–13.
30. Li, S. Y., Rong, M., Grieu, F., & Iacopetta, B.(2006). PIK3CA mutations in breast cancer are associated with poor outcome. Breast cancer research and treatment, 96(1), 91-95
31. Black, J. D., Lopez, S., Cocco, E., Bellone, S.,Altwerger, G., Schwab, C. L., & Santin, A. D.(2015). PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas. British journal of cancer, 113(7), 1020-1026.
32. Oda, K., Okada, J., Timmerman, L., RodriguezViciana, P., Stokoe, D., Shoji, K.& McCormick, F. (2008). PIK3CA cooperates with other
phosphatidylinositol 3′-kinase pathway mutations to effect oncogenic transformation. Cancer research, 68(19), 8127-8136.
33. Gymnopoulos, M., Elsliger, M. A., & Vogt, P. K. (2007). Rare cancer-specific mutations in PIK3CA show gain of function. Proceedings of
the National Academy of Sciences, 104(13),5569-5574.
34. Li, J., Jeong, K. J., Shao, S., Chen, H., Tsang, Y.H., & Mills, G. B. (2018). Systematic functional annotation of somatic mutations in
cancer. Cancer cell, 33(3), 450-462
2. Zhang, D., Yuan, Y., Zhu, J., Zhu, D., Li, C., Cui, W., ... & Liu, B. (2021). Insulin‑like growth factor 1 promotes neurological functional recovery after spinal cord injury through inhibition of autophagy via the PI3K/Akt/mTOR signaling pathway. Experimental and Therapeutic Medicine, 22(5), 1-9.
3. Chen, J. (2012). Roles of the PI3K/Akt pathway in Epstein-Barr virus-induced cancers and therapeutic implications. World journal of
virology, 1(6), 154.
4. Elwy, F.; Helwa, R.; El Leithy, A.A.; Shehab El din, Z.; Assem, M.M.; Hassan, N.H. PIK3CA mutations in HER2-positive Breast Cancer
Patients; Frequency and Clinicopathological Perspective in Egyptian Patients. Asian Pac. J. Cancer Prev. 2017, 18, 57–64
5. Barbareschi, M.; Buttitta, F.; Felicioni, L.; Cotrupi, S.; Barassi, F.; Del Grammastro, M.; Ferro, A.; Dalla Palma, P.; Galligioni, E.;
Marchetti, A. Di_erent prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin. Cancer Res. 2007, 13, 6064–6069.
6. Ding,W.J.; Zeng, T.;Wang, L.J.; Lei, H.B.; Ge,W.;Wang, Z. Genes with mutation significance were highly associated with the clinical pattern of patients with breast cancer. Oncotarget 2017, 8, 98094–98102.
7. Hu, Z.Y.; Xie, N.; Tian, C.; Yang, X.; Liu, L.; Li, J.; Xiao, H.;Wu, H.; Lu, J.; Gao, J.; et al. Identifying Circulating
8. Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance. EBioMedicine 2018, 32, 111–118.
9. Perez-Tenorio, G.; Alkhori, L.; Olsson, B.; Waltersson, M.A.; Nordenskjold, B.; Rutqvist, L.E.; Skoog, L.;Stal, O. PIK3CA mutations and
PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin. Cancer Res. 2007, 13, 3577–3584. [CrossRef] [PubMed]
10. Cizkova, M.; Susini, A.; Vacher, S.; CizeronClairac, G.; Andrieu, C.; Driouch, K.; Fourme, E.; Lidereau, R.; Bieche, I. PIK3CA mutation impact on survival in breast cancer patients and in ERalpha, PR and ERBB2-based subgroups. Breast Cancer Res. 2012, 14, R28
11. Wigedan, N. AL-Moosawi, 2017. The relation of TEL-AML1 fusion genes, mutantP53 gene&B19 parvovirus infection in newly diagnosed pediatric Acute Lymphoblastic Leukemia, in Basrah. M.Sc. thesis medical mirobiology. Ch3: 66.
12. Vogt PK, Hart JR, Gymnopoulos M, Jiang H, Kang S, Bader AG, Zhao L, Denley A. Phosphatidylinositol 3-kinase: the oncoprotein. Curr Top Microbiol Immunol. ??????
13. Gulley, M. L. (2001). Molecular diagnosis of Epstein-Barr virus-related diseases. The Journal of molecular diagnostics, 3(1), 1-10.
14. Lee, M. A., Hong, Y. S., Kang, J. H., Lee, K. S., You, J. Y., Lee, K. Y., & Park, C. H. (2004). Detection of Epstein-Barr virus by PCR and
expression of LMP1, p53, CD44 in gastric cancer. The Korean journal of internal medicine, 19(1), 43.
15. Bachman, K.E.; Argani, P.; Samuels, Y.; Silliman, N.; Ptak, J.; Szabo, S.; Konishi, H.; Karakas, B.; Blair, B.G.; Lin, C.; et al. The
PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol. Ther. 2004, 3,772–775. [CrossRef]
16. Saal, L.H.; Holm, K.; Maurer, M.; Memeo, L.;Su, T.;Wang, X.; Yu, J.S.; Malmstrom, P.O.; Mansukhani, M.; Enoksson, J.; et al. PIK3CA
mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast
carcinoma. Cancer Res. 2005, 65, 2554–2559
17. Liu, P., Cheng, H., Roberts, T. M., & Zhao, J. J. (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nature reviews Drug discovery, 8(8), 627-644.
18. Janku, F. (2017). Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From laboratory to patients. Cancer treatment
reviews, 59, 93-101.
19. Kalinsky, K., Jacks, L. M., Heguy, A., Patil, S., Drobnjak, M., Bhanot, U. K., ... & Moynahan, M. E. (2009). PIK3CA Mutation Associates with Improved Outcome in Breast CancerPIK3CA Mutation and Improved Outcome in Breast Cancer. Clinical cancer research, 15(16), 5049- 5059
20. Mosele, F., Stefanovska, B., Lusque, A., Dien, A. T., Garberis, I., Droin, N.,& André, F. (2020). Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Annals of Oncology, 31(3), 377-386.
21. Chen, J. (2012). Roles of the PI3K/Akt pathway in Epstein-Barr virus-induced cancers and therapeutic implications. World journal of
virology, 1(6), 154.
22. Liang J, Slingerland JM. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle. 2003;2:339–345.
23. Mukohara, T. (2015). PI3K mutations in breast cancer: prognostic and therapeutic implications. Breast Cancer: Targets and Therapy, 7, 111.
24. Samuels, Y.; Diaz, L.A.; Schmidt-Kittler, O.; Cummins, J.M.; Delong, L.; Cheong, I.; Rago, C.; Huso, D.L.; Lengauer, C.; Kinzler, K.W.; et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 2005,7, 561–573.
25. Huayu Hu, Junyong Zhu, Yuting Zhong, Rui Geng, Yashuang Ji, Qingyu Guan, et al . PIK3CA mutation confers resistance to chemotherapy in triple-negative breast cancer by inhibiting apoptosis and activating the PI3K/AKT/mTOR signaling pathway. Ann Transl Med 2021;9(5):410 | http://dx.doi.org/10.21037/atm-21-698
26. Karakas, B.; Bachman, K.E.; Park, B.H. Mutation of the PIK3CA oncogene in human cancers. Br. J. Cancer 2006, 94, 455–459.
27. Rand, A.; Yardena, S. PIK3CA in cancer: The past 30 years. Semin. Cancer. Biol. 2019, 59, 36–49
28. Paola Fuso 1,* , Margherita Muratore 1, Tatiana D’Angelo 2, Ida Paris 1 , Luisa Carbognin 1,Giordana Tiberi 1,et al.PI3K Inhibitors in
Advanced Breast Cancer: The Past, The Present,New Challenges and Future Perspectives.Cancers 2022, 14, 2161 :1-21
29. Bizhani F, Hashemi M, Danesh H, Nouralizadeh A, Narouie B,Bahari G, et al. Association between single nucleotidepolymorphisms in the PI3K/AKT/mTOR pathway and bladdercancer risk in a sample of Iranian population. EXCLI J2018;17:3–13.
30. Li, S. Y., Rong, M., Grieu, F., & Iacopetta, B.(2006). PIK3CA mutations in breast cancer are associated with poor outcome. Breast cancer research and treatment, 96(1), 91-95
31. Black, J. D., Lopez, S., Cocco, E., Bellone, S.,Altwerger, G., Schwab, C. L., & Santin, A. D.(2015). PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas. British journal of cancer, 113(7), 1020-1026.
32. Oda, K., Okada, J., Timmerman, L., RodriguezViciana, P., Stokoe, D., Shoji, K.& McCormick, F. (2008). PIK3CA cooperates with other
phosphatidylinositol 3′-kinase pathway mutations to effect oncogenic transformation. Cancer research, 68(19), 8127-8136.
33. Gymnopoulos, M., Elsliger, M. A., & Vogt, P. K. (2007). Rare cancer-specific mutations in PIK3CA show gain of function. Proceedings of
the National Academy of Sciences, 104(13),5569-5574.
34. Li, J., Jeong, K. J., Shao, S., Chen, H., Tsang, Y.H., & Mills, G. B. (2018). Systematic functional annotation of somatic mutations in
cancer. Cancer cell, 33(3), 450-462
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Mar 13, 2023
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Rasha N. Jawad, Hassan J. Hasony, & Jasim Al- Diab. (2023). PI3K pathway gene polymorphismin breast cancer tissues proliferation with synergistic effect of EBV- LMP1 oncogene activity among breastcancer patients in Basrah, southern of Iraq. Journal of Population Therapeutics and Clinical Pharmacology, 30(3), 265–272. https://doi.org/10.47750/jptcp.2023.30.03.028
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