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Oncogenomics: Clinical Pathogenesis Approach International Journal of Genetics, ISSN: 0975–2862, Volume 1, Issue 2, 2009, pp-25-43 Oncogenomics: Clinical pathogenesis approach Gupta G. 1, Gupta N. 2, Trivedi S. 3, Patil P. 5, Gupta M. 2, Jhadav A. 4, Vamsi K.K.6, Khairnar Y. 4, Boraste A. 4, Mujapara A.K. 7, Joshi B.8 1S.D.S.M. College Palghar, Mumbai 2Sindhu Mahavidyalaya Panchpaoli Nagpur 3V.V.P. Engineering College, Rajkot, Gujrat 4Padmashree Dr. D.Y. Patil University, Navi Mumbai, 400614, India 5Dr. D. Y. Patil ACS College, Pimpri, Pune 6Rai foundations College CBD Belapur Navi Mumbai 7Sir PP Institute of Science, Bhavnagar 8Rural College of Pharmacy, D.S Road, Bevanahalli, Banglore Abstract - Oncogenomics is new research sub-field of genomics, which applies high throughput technologies to characterize genes associated with cancer and synonymous with cancer genomics. The goal of oncogenomics is to identify new oncogenes or tumor suppressor genes that may provide new insights into cancer diagnosis, predicting clinical outcome of cancers, and new targets for cancer therapies. Oncoproteomics is the term used to describe the application of proteomic technologies in oncology and parallels the related field of oncogenomics. It is now contributing to the development of personalized management of cancer. Genomics has generated a wealth of data that is now being used to identify additional molecular alterations associated with cancer development. Mapping these alterations in the cancer genome is a critical first step in dissecting oncological pathways. Keywords - Biomarkers, Drug development, Drug resistance, Gene therapy, Oncogenomics Introduction Oncogenomics applies high throughput technologies to characterize genes associated transducing cellular signals of cell growth or with cancer and is used to identify new death. In particular, more than 50% of colorectal oncogenes or tumor suppressor genes, which cancers were found to carry a mutation in a may provide new insights into cancer diagnosis, kinase or phosphatase gene. predicting clinical outcome of cancers and new Phosphatidylinositold 3-kinases (PIK3CA) gene targets for cancer therapies. The success of encode for lipid kinases which were identified to targeted cancer therapies such as Gleevec, commonly contain mutations in colorectal, breast, Herceptin and Avastin raised the hope for gastric, lung, and various other types of cancer oncogenomics to elucidate new targets for [4, 5]. The oncogenomics can be used most cancer research [1]. Oncogenomics is to allow for effectively to impact the clinical response to the development of personalized cancer cancer and in advances in the clinical application treatment and focuses on the genomic, of pharmacogenomics to predict response to epigenomic and transcript level alterations in oncology therapeutic in cancer paradigm [6]. cancer. Comparative oncogenomics uses cross- Human cancer genomes are characterized by species comparisons to identify oncogenes and numerous chromosomal aberrations of uncertain research involves studying cancer genomes, pathogenetic significance. Here, in an inducible transcriptomes and proteomes in other model mouse model of melanoma, the characterized organisms, i.e., mice, identifying potential metastatic variants with an acquired focal oncogenes, and referring back to human cancer chromosomal amplification that corresponds to a samples to see whether homologues of these much larger amplification in human metastatic oncogenes are also important in causing cancer melanomas. Further research identified Nedd9, in humans. Comparative oncogenomics is a an adaptor protein related to p130CAS, as the powerful approach to oncogene identification [2]. only gene within the minimal common region that Mutational analysis of all gene families has been exhibited amplification - associated a powerful approach to oncogenomics, which has overexpression. Functional, clinical and been informative. Genes from same family have biochemical studies established NEDD9 as a similar functions, as predicted by similar coding bona fide melanoma metastasis gene. NEDD9 sequences and protein domains, have been enhanced invasion invitro and metastasis invivo systematically sequenced in cancerous genomes of both normal and transformed melanocytes, to identify particular pathways which may be functionally interacted with focal adhesion kinase associated with cancer progression. Such class and modulated focal contact formation, and of families has been studied is the kinase family exhibited frequent robust overexpression in genes, involved in adding phosphate groups to human metastatic melanoma relative to primary proteins, and phosphatase family genes, involved melanoma. Comparative oncogenomics has with removing phosphate groups from proteins. enabled the identification and facilitated the [3]. The kinase and phosphatase families were validation of a highly relevant cancer gene first examined because of their apparent role in Copyright © 2009, Bioinfo Publications, International Journal of Genetics, ISSN: 0975–2862, Volume 1, Issue 2, 2009 Oncogenomics: Clinical pathogenesis approach governing metastatic potential in human presents a significant challenge. Regional pattern melanoma [7]. recognition approaches, the most probable copy number–dependent regions and 50 potential Oncogenomics and its application to clinical driver genes. The gene selection process, the pathogenesis functional relevance of the selected genes was Anaplastic thyroid carcinoma (ATC) is considered evaluated by estimating the prognostic one of the most aggressive malignancies, having significance of the selected genes. Small a poor prognosis and being refractory to interference RNA mediated knockdown conventional chemotherapy and radiotherapy. experiments showed proof-of-principle evidence Alteration in histone deacetylase (HDAC) activity for the potential driver roles of the genes in has been reported in cancer, thus encouraging hepatocellular carcinoma progression (i.e., the development of HDAC inhibitors, whose NCSTN and SCRIB). More to this, systemic antitumor action has been shown in both solid prediction of drug responses implicated the and hematological malignancies [8]. Genome association of the 50 genes with specific having huge amount of information about signaling molecules (mTOR, AMPK, and EGFR) biological functions and the interest is now [12]. Study on retroviral insertion mutagenesis directed to the study using genomic information, has recently received much attention because of the genomic strategy is not clearly understood. its adverse effects in the application of retroviral The following 4 studies are new strategy for vector-based gene therapy, resulting in leukemia research: (i) models for genetic and genomic in certain patients. Increasing numbers of new investigations of complex genetic diseases (ii) potential oncogenes identified in retroviral Molecular classification by global gene screens have given a valuable basis for a better expression profiling (iii) Functional genomics understanding of cancer related pathways in search of disease-related genes using mice. Important challenges that now lie ahead microarrays (iv) Acute ischemic change of are (i) to determine the relevance and causal mRNA expression [9]. Poly-trauma remains a relationship of these genes with various types of medical entity with major implications, for human cancer (ii) to develop strategies to identify patient's mortality, morbidity and healthcare tumor suppressor genes on a large scale, (iii) to economics. Advances in molecular medicine place the disease genes into regulatory networks have improved diagnostic techniques in detecting to better understand their role in the complex devastating complication after major trauma. pathogenesis of cancer, and (iv) to determine Patients at high risk of multiple organ dysfunction their value for diagnosis refinement and syndrome (MODS) or adult respiratory distress therapeutic target intervention in human disease syndrome (ARDS), could be identified early, [13]. High population frequency of a germline monitored and treated. Proteomics research is TP53 mutation (R337H) predisposing to early the systematic evaluation of proteins produced by cancer has led to mass newborn testing for this the cell under normal or pathological mutation. Newborn screening for inherited cancer circumstances. Investigating protein production research risk is complex and controversial. will allow us to identify and modify disease R337H has been identified in Brazilian families natural history and treatment [10]. Early detection with Li-Fraumeni or related syndromes is essential for the control and prevention of predisposing to cancers in childhood (i.e., brain, many diseases, in cancer, which is the reason renal, and adrenocortical carcinomas), why the need for new disease markers with adolescence (i.e., soft tissue and bone improved sensitivity and specificity continues to sarcomas), and young adulthood (i.e., breast grow. Utilization of sophisticated bioinformatics cancer). Detailed assessment of the risks, tools enables the increased specificity and a benefits, and costs is needed to ensure that relatively large quantity of high quality assays for medical, social, and ethical justifications for any gene of interest. Genetic research screening newborn screening are met [14]. Caveolin-1 is is one of the fastest moving areas of medical the main component of caveolae membrane science, particularly in oncology, and as more structures has different roles during genes are cloned, and more disease-associated
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