- Volume 16 Issue 8
DOI QR Code
High Frequency of Codon 12 but not Codon 13 and 61 K-ras Gene Mutations in Invasive Ductal Carcinoma of Breast in a South Indian Population
- Sushma, C (Department of Genetics, Asian Institute of Gastroenterology) ;
- Prasad, Shiva (Department of Genetics, Asian Institute of Gastroenterology) ;
- Devi, Rudrama (Department of Genetics, Asian Institute of Gastroenterology) ;
- Murthy, Sudha (Department of Pathology, Indo-American Cancer Hospital) ;
- Rao, TS (Department of Pathology, Indo-American Cancer Hospital) ;
- Naidu, CK (Department of Surgical Oncology, Indo-American Cancer Hospital)
- Published : 2015.04.29
Background: Ras genes are thought to play an important role in human cancer since they have been found to be activated frequently in several types of tumors including breast cancer, where the overall incidence of K-RAS oncogene activation is 0-10%. Evaluation of K-RAS gene not only for mutational frequency but also for mutation types in this downstream signaling gene pathway is necessary to determine the mechanisms of action. The present study was conducted to test the hypothesis that K-RAS activation is involved in breast cancer risk of south Indian population. Materials and Methods: A total of 70 paired pathologically confirmed tumor and non-tumor tissues from the same breast cancer patients were analysed for most common K-RAS mutations of codon 12,13 and 61 by polymerase chain reaction followed by restriction digestion and direct nucleotide sequencing method. Results: We found that a high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in this study. Conclusions: Our study indicated that only codon 12 may be involved in initiating breast carcinogenesis in India.
Breast cancer;K-ras mutations;risk;South India
- Agnantis NJ, Petraki C, Markoulatos Ρ, Spandidos DA (1986). Immunohistochemical study of the raj oncogene expression in human breast lesions. Anticancer Res, 6, 1157-60.
- Baldus SE, Schaefer KL, Engers R, et al (2010). Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res, 16, 790-9. https://doi.org/10.1158/1078-0432.CCR-09-2446
- Chan IT, Kutok JL, Williams IR, et al (2004). Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J Clin Invest, 113, 528-38. https://doi.org/10.1172/JCI20476
- Chaiyapan W, Duangpakdee D, Boonpipattanapong T, Kanngern S, Sangkhathat S (2013). Somatic mutations of K-Ras and BRAF in Thai colorectal cancer and their prognostic value. Asian Pac J Cancer Prev, 14, 329-32. https://doi.org/10.7314/APJCP.2013.14.1.329
- De Roock W, Jonker DJ, Di Nicolantonio F, et al (2010). Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA, 304, 1812-20. https://doi.org/10.1001/jama.2010.1535
- Dickson RB, Gottardis MM, Merlino GT (1991). Molecular insights into breast cancer from transgenic mouse models. Bioessays, 13, 591-6. https://doi.org/10.1002/bies.950131109
- Jakovljevic K, Malisic E, Cavic M, et al (2012). KRAS and BRAF mutations in Serbian patients with colorectal cancer. J BUON, 17, 575-80.
- Kasid A, Lippman ME, Papageorge AG, et al (1985). Transfection of v-rasH DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity. Science, 228, 725-8. https://doi.org/10.1126/science.4039465
- Kooshyar MM, Ayatollahi H, Keramati MR, et al (2013). Lack of KRAS gene mutations in chronic myeloid leukemia in Iran. Asian Pac J Cancer Prev, 14, 6653-56. https://doi.org/10.7314/APJCP.2013.14.11.6653
- Mansi L, Viel E, Curtit E, Medioni J, Le Tourneau C (2011). Targeting the RAS signalling pathway in cancer. Bulletin Du Cancer, 98, 1019-28.
- McCubrey JA, Steelman LS, Abrams SL, et al (2008). Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia, 22, 708-22. https://doi.org/10.1038/leu.2008.27
- Nagasaka T, Sasamoto H, Notohara K, et al (2004). Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol, 22, 4584-94. https://doi.org/10.1200/JCO.2004.02.154
- Pereira CBL, Leal MF, de Souza CRT, et al (2013). Prognostic and predictive significance of MYC and KRAS alterations in breast cancer from women treated with neoadjuvant chemotherapy.
- Prosperi MT, Dupre G, Lidereau R, Goubin G (1990). Point mutation at codon 12 of the K-ras gene in a primary breast carcinoma and the MDA-MB-134 human mammary carcinoma cell line. Cancer Lett, 51, 169-74. https://doi.org/10.1016/0304-3835(90)90053-Z
- Rochlitz CF, Scott GK, Dodson JM, et al (1989). Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer. Cancer Res, 49, 357-60.
- Shemirani AI, Haghighi MM, Milanizadeh S, et al (2011). The role of kras mutations and MSI status in diagnosis of colorectal cancer. Gastroenterol Hepatol Bed Bench, 4, 70-5.
- Sommers CL, Papageorge A, Wilding G, et al (1990). Growth properties and tumorigenesis of MCF-7 cells transfected with isogenic mutant of rasH. Cancer Res, 50, 67-71.
- Spandidos DA (1987). Oncogene activation in malignant transformation: a study of Η-ras in human breast cancer. Anticancer Res, 7, 991-6.
- Spandidos DA, Agnantis NJ (1984). Human malignant tumors of the breast, as compared to their respective normal tissue, have elevated expression of the Harvey ras oncogene. Anticancer Res, 4, 269-72.
- Stricker TP, Kumar V (2012). In: Kumar V, Abbas AK, Fausto N, Aster JC, editors (2012). Robbins and cotran pathologic basis of disease. 8th ed. Philadelphia: Saunders Elsevier, 259-320.
- Sukumar S, Carney W , Barbacid M (1988). Independent molecular pathways in initiation and loss of hormone responsiveness of breast carcinomas. Science, 240, 524-6. https://doi.org/10.1126/science.3282307
- Takao Asai, Ernesto Loza, Guido Villa-Gomez Roig, et al (2014). High frequency of TP53 but not K-ras gene mutations in bolivian patients with gallbladder cancer. Asian Pac J Cancer Prev, 15, 5449-54. https://doi.org/10.7314/APJCP.2014.15.13.5449
- Tejpar S, Celik I, Schlichting M, et al (2012). Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol, 30, 3570-77. https://doi.org/10.1200/JCO.2012.42.2592
- Tong L, Yang X-Y, Liu M-F, et al (2012). Mutational analysis of key EGFR pathway genes in chinese breast cancer patients. Asian Pac J Cancer Prev, 13, 5919-23.
- Zhu X, Li Y, Luo X, Fei J (2012). Inhibition of small GTPase RalA regulates growth and arsenic-induced apoptosis in chronic myeloid leukemia (CML) cells. Cellular Signalling, 24, 1134-40. https://doi.org/10.1016/j.cellsig.2012.01.016