Role of Gene Silencing in the Development of Cancer - Essay Example

Running Head: Role of Gene Silencing in the Development of Cancer Role of Gene Silencing in the Development of Cancer of the Under the guidance of University AHA format Date of submission Abstract The role of gene silencing in the development of various cancers is a much researched topic these days. There are reports that alteration of certain genomes related to cancer suppression can result in silencing of genetic expression of these genes resulting in development of cancer. Characterization of such genes has evolved hope in the management of cancer. It has been proposed that detection of gene silencing in certain genes which are characteristic of tumors can help not only in early detection, but also may enhance the development of novel therapies for cancer. In this research, review of literature pertaining to gene silencing and development of cancer was conducted. The articles were retrieved from PUBMED using suitable terms. Qualitative analysis of the results proved that gene silencing plays a significant role on the development of various cancers. It can thus be concluded that gene silencing through alteration of certain components of tumor suppression genes is one of the means of development of cancers and further research in this aspect may provide information for early detection and novel management of cancers. Back ground and rationale The soaring rates of cancer has made experts extend their research to ascertain various changes in DNA of certain genes. This is with an intention to know the various mechanisms of evolution of each type of tumor. Understanding of the development of tumor helps in the radical detection of cancer. Recent reports have suggested the importance of both genetic and epigenetic events in the evolution of cancer1. Extensive research has led to the discovery of gene silencing and its role in cancer progression. Various screening methods for cancer with respect to genetic alterations, which are available as of now are not universal tumor markers and thus early detection becomes difficult2. Research has shown that certain alterations like hypermethylation of certain parts of the gene the gene promoters, cause silencing of tumor suppression and this mechanism can be used for universal screening . Currently, further research is in progress to use gene silencing as a molecular marker for early detection of cancer. Gene silencing is one of the mechanisms of gene regulation during which the expression of gene is either interrupted or suppressed at transcriptional or translational levels. For the past 30 years, researchers have been working on manual methods of gene silencing as a mode of treatment for some diseases. Current research has identified the role of gene silencing in the development of certain cancers, especially in non-familial types of colon cancer and renal cancer. This has interested the experts because unlike mutation, gene silencing is reversible; and theoretically it means that reversal of gene silencing should stop the progression of cancer2. Thus identification of gene silencing of tumor progression genes in cancer has 2 purposes: 1. Molecular marker for early detection of cancer. 2. Possibility of treatment due to reversal of gene slicing. With this back ground, I intend to review literature pertaining to the role of gene silencing in cancer progression. Methods Search for this project was done on electronic database PUBMED. For the purpose of retrieval of articles, a combination of the terms "gene silencing" and "hypermethylation" with "cancer genes" and "tumor genes" were used. It was found that numerous articles were available. The limits used for the search were "full text articles", "articles after 2000", and "articles only in English". For the purpose of this review, I went through the abstracts of the journals and picked up five of them, each of them studying gene silencing on different tumor types. After reviewing these article, I formulated the results and elaborated the discussion to enhance the understanding of this research. Results Mokarram, Kumar and Brim3 studied gene silencing of a set of genes known as Candidate Cancer Genes or CAN genes of colorectal cancer in 51 Iranians and 51 African-Americans. They found that in both the populations, more than 65% gene silencing in the form of hypermethylation was noted in certain genes and in another set of genes, gene silencing was less than 50%. The researchers also found that while 31% of the tumors in African -American population showed gene silencing in a particular group of genes, only 28% of Iranian genes demonstrated these changes. These differences have been attributed to the differences in cancer progression observed clinically in both the populations. Martin-Subero et al4 studied gene silencing in 367 blood and lymphoid tissue- related cancers. In their study, the researchers found that gene silencing was more prominent and frequent in lymphoid malignancies than in myeloid malignancies. They also found a high correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Karray-Chouayekh, et al5 evaluated the gene silencing patterns of 2 genes which are related to colon cancer and breast cancer. The authors found that the frequencies of gene silencing in the former was 24.36% and that for the latter was 46%. In the same study, the researchers also deducted that gene silencing of a particular gene was highly correlated with a particular gene expression and overall survival. This proves the role of gene silencing as an useful indicator of poor prognosis of breast cancer. Hesson et al6 characterized the expression of a set of genes called RASSF10, whose family members have been known to be inactivated in several cancer types. The characterization was done in normal human bone marrow. The authors found that gene silencing of these genes is a distinct feature in childhood leukemias. Vladimirova et al7 studied characterization of LHX9 gene in patients with a type of brain tumor. They found that gene silencing of this gene occurred at two specific regions and was associated with reduced messenger RNA expression. Another interesting feature of this study is that the researchers were able to reverse gene silencing using a drug. Thus it is hoped that reversal of gene silencing can be a novel therapeutic approach to pediatric glioma. Discussion It is evident from the analysis of the above studies that gene silencing of tumor suppression genes can contribute to the development of cancer. Evaluation of gene silencing can provide information on not only cancer development, but also on the aggressiveness of the tumor and prognosis. Mokarram et al3 concluded that CAN genes are useful markers for colon carcinogenesis and that the differences in gene silencing was the reason for the higher incidence and aggression of colorectal cancer in African-American population. In the study by Martin-Subero et al4, it was found that the silenced genes play a major role in the development of different types of blood cancers. Karray-Chouayekh, et al5 study suggested that silencing of genes could be used as an indicator of poor prognosis of breast cancer. Hesson et al6 proved that gene silencing of RASSF was associated with childhood leukemias. The study by Vladimirova et al7 raised hopes for novel treatment of brain cancer by reversal of gene silencing by drugs. Conclusion From this research it is evident that identification of gene silencing is a potential sensitive marker that can help define cancer-risk states, assist in the monitoring of preventive strategies, help in early diagnosis and detection, and estimate the prognosis of cancer. References 1. Baylain, SB, Herman, JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet. 2000; 16(4):168-74. 2. Esteller, M, Corn, PG, Baylin, SB, Herman, JG. A Gene Hypermethylation Profile of Human Cancer. Cancer Research. 2001; 61: 3225-3229. 3. Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberi-firoozi M, Nouraie M, Green R, Lee E, Smoot DT, Ashktorab H. Distinct high-profile methylated genes in colorectal cancer. PLoS One. 2009;4(9):e7012. 4. Martin-Subero JI, Ammerpohl O, Bibikova M, Wickham-Garcia E, Agirre X, Alvarez S, Brüggemann M, Bug S, Calasanz MJ, Deckert M, Dreyling M, Du MQ, Dürig J, Dyer MJ, Fan JB, Gesk S, Hansmann ML, Harder L, Hartmann S, Klapper W, Küppers R, Montesinos-Rongen M, Nagel I, Pott C, Richter J, Román-Gómez J, Seifert M, Stein H, Suela J, Trümper L, Vater I, Prosper F, Haferlach C, Cruz Cigudosa J, Siebert R. A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms. PLoS One. 2009;4(9):e6986. 5. Karray-Chouayekh S, Trifa F, Khabir A, Boujelbane N, Sellami-Boudawara T, Daoud J, Frikha M, Gargouri A, Mokdad-Gargouri R. Clinical significance of epigenetic inactivation of hMLH1 and BRCA1 in Tunisian patients with invasive breast carcinoma. J Biomed Biotechnol. 2009;2009:369129. 6. Hesson LB, Dunwell TL, Cooper WN, Catchpoole D, Brini AT, Chiaramonte R, Griffiths M, Chalmers AD, Maher ER, Latif F. The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias. Mol Cancer. 2009; 8:42. 7. Vladimirova V, Mikeska T, Waha A, Soerensen N, Xu J, Reynolds PC, Pietsch T. Aberrant methylation and reduced expression of LHX9 in malignant gliomas of childhood. Neoplasia. 2009; 11(7):700-11. Read More