Genomics is a comprehensive study of the whole genome, genetic products, and their interactions. Human genome project has identified around 25,000-30,000 genes, and prevailing presence in tumor pathogenesis, high number of mutations, epigenetic changes, and other gene disorders have been identified. Microarrays technology is used for the analysis of these changes. Postgenome age has begun, and the initial results ensure the improvement of molecular tumor diagnostics and the making of a new taxonomic tumor classification, as well as the improvement, optimization and individualization of anti-tumor therapy. First genomic classifications have been made of leukemias, non-Hodgkin lymphoma, and many solid tumors. For example, 4 molecular types of breast carcinoma, three types of diffuse B cell lymphoma, two types of chromophobic renal carcinoma have been identified. Also, gene structures for favorable and unfavorable outcome in leukemia, breast cancer, prostate, bronchi, and other tumors have been identified. It is absolutely possible to diagnose the primary outcome of tumors with which standard tumor position may not be proved using standard diagnostic tools. Pharmacogenomic profiles have ensured better definition of interindividual differences during therapy using antineoplastic drugs and the decrease of their toxicity, as well as individual treatment approach and patient selection with which favorable clinical outcome is expected. Pharmacogenomics has impacted the accelerated development of target drugs, which have showed to be useful in practice. New genomic markers mtDNA, meDNA, and miRNA have been identified, which, with great certainty, help the detection and diagnostics of carcinoma. In the future, functional genomics in clinical oncology provides to gain knowledge about tumor pathogenesis; it will improve diagnostics and prognosis, and open up new therapeutic options.
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Quackenbush J. Microarray analysis and tumor classification. N Engl J Med 2006; 354: 2463-72.
Abdullah-Sayani A De Mesquita JMB Van de Vijver MJ. Technology insight: tuning into the genetic orchestra using microarrays-limitations of DNA microarrays in clinical practice. Nature Clinical Medicine 2006; 3 (9): 501-16.
Hunter T. Protein kinases and disease in the postgenomic era. http://pasteur.fr/applications/eurocont/proteinkinase/14hunterabstract.pdf
Bernner Ch Duggan D. Oncogenomics. Molecular approach to cancers. USA Arizona Totoma New Jersey: Humana Press; 2004.
Liu ET Krishna R Karturi R. Microarrays and clinical investigations. N Engl J Med 2004; 350: 1505-97.
Landanyi M Gerald WL. Expression profiling of human tumors. Diagnostic and research applications. Human Press USA; 2003.
Ramaswamy S. Translating cancer genomics into clinical oncology. N Engl J Med 2004; 350: 1814-7.
Fey MF. Genomics and proteomics: expression arrays in clinical oncology. Ann Oncol 2004; Suppl 4:iv163-5.
Wadlow R Ramaswamy. DNA microarrays in clinical cancer research. Current Molecular Medicine 2005; 5: 111-20.
Gabriele I Moreti F Pierotti MA Marncola FM Foa R Belardelli FM. The use of microarray technologies in clinical oncology. J Translation Medicine 2006; 4: 1-5.
Report of working group on biomedical technology February 2005. Recommendation for Human Cancer Genome Project. http://www.genome.gov/pages/about/NACHGR/may
Goldsmith ZG Danasekeran N. The microevolution: applications and impacts of microarray technology on molecular biology and medicine (review). Int J Molec Med 2004;13: 483-95.
Weaver ChH Deutrer D. Medical genomics: implications for clinical oncology. Current Topics in Oncology 2005.
Nambiar PR Boutin SR Raja R Rosenberg DW. Global gene expression profiling: a complement to conventional histopathologic analysis of neoplasia. Veterinary Pathology 2005; 42: 735-52.
Stoeckert CJ Jr Causton HC Ball CA. Microarray databases: standards and ontologies. Nat Genet 2002; 32: 469-73.
Brazma A Hingamp P Quackenbush J Sherlock G Spelman P Stoeckert CJ Jr et al. Minimum information about a microarray experiment (MIAME) - toward standards for microarray data. Nat Genet 2001; 29: 365-71.
loanidis JPA. A rapid map for efficient and reliable human genome epidemiology. Nat Genet 2006; 38: 3-5.
Grimwade D Haferlach T. Gene expression profiling in acute myeloid leukemia. N Engl J Med 2004; 350; 16: 1676-8.
Xiong H Chen YW. Kernel-based distance metric learning for microarray data classification. BMC Bioinformatics 2006; 7: 299.
Yeoh EJ Ross ME Shirtleff SA Williams WK Patelo D Mahariz R et al. Classification subtype discovery and prediction of outcome in pediatric acute lymphoblastic leukemia by gene profiling. Cancer Cell 2002; 1 (2): 133-43.
Bench AJ Erber WN Scott MA. Molecular genetic analysis of haematological malignancies: Acute leukemias and myeloproliferative disorders. Clin Lab Haematol 2005; 27 (3): 148.
Willson C Davidson GS Martin SB Andries E Potter J Harvary R et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood 2006; 108 (2): 685-96.
Mrozek K Bloomfied CD. Chromosome aberrations gene mutations and expression changes and progression in adult AML. Hematology 2006; 1: 169-77.
Houghton SG Cockerill FR. Real-time PCR: overview and applications. Surgery 2006; 191 (1): 1-5.
Lee WI Kantarijan H Glasman A Talpaz M Lee MS. Quantitative measurement of BCR/abl transcripts using real-time polymerase chain reaction. Ann Oncol 2002; 13: 781-8.
Tefferi A Dewald GW Litzow ML et al. Chronic myeloid leukemia: current application of cytogenetics and molecular testing for diagnosis and therapeutic. Mayo Clin Proc 2005; 80 (30): 390-402.
Colin GA Ferracin A Cimmino A et al. A micro RNA signature associated with prognosis and progression in chroniclymphocytic leukemia. N Engl J Med 2005; 353: 1793-801.
Mirshahid HR Abraham J. Genomic profiling in clinical oncology. Postgraduate Medicine 2006; 119 (2): July-August.
Zhan F Huang Y Colla S Stewart JP Hanamura I Gupta S et al. The molecular classification of multiple myeloma. Blood 2006; 108: 2020-8.
Bea S Zefl X Wright G et al. Diffuse large B cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene expression based survival prediction. Blood 2005; 106 (9): 3183-90.
Studt LM. Molecular diagnosis of the hematological cancers. N Engl J Med 2003; 348 (18): 1777-85.
Pasgualucci L Compagno M Holdsworth J et al. Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. N Engl J Med 2006; 354 (2): 311-17.
Polsen CB Broup R Nielsen FC Borregoard N Hansen M Gronbaek K et al. Microarray-based classification of diffuse large B-cell lymphoma. Eur J Hematol 2005; 74 (6): 453.
Savage KJ Monti S Kutok JL Cattoretti G Neubarger D De Leval L et al. The molecular signature of mediastinal large B cell lymphoma diffuse from that of other diffuse large B-cell lymphomas and their features with classical Hodgkin lymphoma. Blood 2003; 102 (13): 3871-9.
Suguro M Tagava H Kagoma Y et al. Expression profiling analysis of the CD5+ diffuse large B cell lymphoma subgroup: development of a CD5 signature. Cancer Sci 2006; 97: 868-74.
Monti S Savage KJ Kutok JK et al. Molecular profiling of diffuse large B cell lymphoma reveals a novel disease subtype with brisk host inflammatory response and distinct genetic features. Blood 2005; 105 (5): 1851-61.
Humnel M Beutnik S Berger H. A biological definition of Burkitt's lymphoma from transcriptional A genome profiling. N Engl J Med 2006; 354 (23): 2419-30.
Connors JM. Improving diagnosis and treatment of lymphomas with gene expression profiling. Hematologist/jfm05/review.8/30/2006
Roberts RA Wright G Rosenwold AR et al. Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B cell lymphoma is highly coordinated and related to poor patient survival. Blood 2006; 88 (1): 311-8.
Schraders M Pfundt R Straatman HM et al. Novel chromosome imbalances in mantle cell lymphoma detected by genome wide array based comparative genomic hybridization. Blood 2005; 105 (4): 1686-93.
Bergamashi A Kym YH Wang P Sorile T Hernandez-Bousard T Longing PE et al. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene expression subtypes of breast cancer. Genes Chromosomes Cancer 2006; 45 (11): 1033-40.
Habel LA Shak S Jacobs MK et al. A population based study: tumor gene expression and risk of breast cancer death among lymph node negative patients. Breast Cancer Res 2006; 8 (3): R 25.
Sorlic T Perou CM Tibshirani R Aas T Geisler S Johansen H et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. PNAS 2001; 98 (19): 10869-74.
Reis-Filho JS Westbury C Pierga JM. The impact of expression profiling on prognostic and predicative testing in breast cancer. J Clin Pathol 2006; 59: 225-31.
Pritchard KI Shepherd LE O'Malley FP et al. HER 2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 2006; 354: 20: 2103-11.
Cheny SH Horng CF West M Huang E Pittmans J Tsou MH et al. Genomic prediction of locoregional recurrence after mastectomia in breast cancer. J Clin Oncol 2006; Oct 01: 4594-4602.
Tonon G Kin-Wong K Maulik G et al. High-resolution genomic profiles of human lung cancer. PNAS 2005; 102: 9625-30.
Raponi M Zhang Y Yu J Chen G Lee G Taylor JMG et al. Gene expression signatures for prediction prognosis of squamous cell and adenocarcinoma of the lung. Cancer Res 2006; 66: 7466-72.
Takeuchi T Tomida S Yatabe Y Kosaka T Osada H Zanagisawa K Mitsudomit T Takahashi T. Expression profile-defined classification of lung adenocarcinoma shows close relationship with underlying major genetic changes and clinicopathologic behaviors. J Clin Oncol 2006; 24 (11): 1679-88.
Albin A Pfeffer U. A new tumor suppressor gene: invasion metastasis and angiogenesis as potential key targets. J Natl Cancer Inst 2006; 98 (12): 800-1.
Granville CA Dennis PA. An overview of lung cancer genomics and proteomics. Am J Resp Cell Mol Biol 2005; 32: 169-76.
Carbone DP. Lung cancer biology and transcription research. Program and abstracts of ASCOI 38th Annual Meeting May 18-21 2002 Orlando Florida Abstract -2.
Rom WN Tchon-Wong KM. Functional genomics in lung cancer and biomarker detection. Am J Resp Cell Molecular Biology 2003; 24: 153-6.
Petty RD Kerr KM Murray GI Nielson MC Rooney PH Bisset D Collie-Duguid ESR. Tumor transcriptome reveals the predicative and prognostic impact of lysosome protease inhibitors in non-small cell lung cancers. J Clin Oncol 2006; 24 (11): 1729-44.
Chen HY Yu SL Chen CH Chang GC Chen CY Yuan A et al. A five-gene signature and clinical outcome in non small-cell lung cancer. N Engl J Med 2007; 356: 11-20.
Battacharyee A Richards WG Staunton J Li C Monti S Vasa P et al. Classification of human lung cancer by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Golub@genome.wi.mit.edu
Liloglou T. DNA methylation profiling in lung cancer. 19th European Association for Cancer Research Congress: Chip-based technologies - Agilent satellite symposium - abstract. July 3rd 2006 Budapest.
Zakovski MF Landanzi M Kris MG. EGFR mutations in small-cell lung cancers in patients who have never smoked. N Engl J Med 2006; 355 (2): 213-5.
Spira A Schmgr F Beane J Shah V Liu G Brody J. Impact of cigarette smoke on the normal airway transcriptome. Chest 2004; 125: 113-S.
Brody J Spira A. State of the art. Chronic obstructive pulmonary disease inflammation and lung cancer. Proc Am Thoracic Society 2006; 3: 535-7.
Potti A Mukherjee S Petersen R Dresman HK Bild A Koontz J et al. A genome strategy of refine prognostic in early stage non-small cell lung cancer. N Engl J Med 2006; avg. 570-80.
Eschrich S Yang I Bloom G et al. Molecular staging for survival prediction of colorectal cancer patients. J Clin Oncol 2005; 23: 3526-35.
Dehl F Dressman D He Y et al. Detection and quantification of mutations in the plasma of patients with colorectal tumours. PNAS 2005102: 45: 16368-73.
Traverso G Shabar A Levin B et al. Detection of APC mutation in fecal DNA from patients with colorectal tumors. N Engl J Med 2002; 346: 311-20.
Nelson W De Marzo A Isaacs WB. Prostate cancer. N Engl J Med 2003; 349: 366-81.
Bueno R Loughlin KR Powell MH Gordon GJ. A diagnostic test for prostate cancer from gene expression profiling data. J Urol 2004; 172 (2 part1): 903-6.
Petersen LE Ozen M Erdem H et al. Artificial neural network analysis of DNA microarray-based prostate cancer recurrence. CIBCB 2005: 1-8.
Hanson JA Gillespie JW Grower A et al. Gene promotion methylation in prostate tumor associated stromal cells. J Natl Cancer Inst 2006; 98 (4): 255-61.
Wang E Panelli MC Zavaglia K et al. Melanomarestricted genes. J Translation Med 2004; 2: 34.
Saldanha G Potter L Da Forno P Pringle JH. Cutaneous melanoma subtypes show different BRAI and NRAS mutations frequencies. Clin Cancer Res 2006; 12: 4499-505.
Mandruzzato S Callegaro A Turcatel G Francescato S Montesco MC Chirian-Silenti V et al. A gene expression signature associated with survival in metastatic melanoma. J Translation Med 2006; 4: 50.
Meltzer PS. Genetic diversity in melanoma. N Engl J Med 2005; 353: 2104-7.
Bauer R Wild PJ Bataille F Pauer A Klinkhammer-Schalke M et al. Prognostic relevance of P-cadherin expression in melanocyte skin tumors analysed by high-throughput tissue microarrays. J Clin Pathol 2006; 59: 699-705.
Nambiar S Hengge UR. Gene expression patterns in melanoma reveal two independent predictors. Workshop: Microarray technologies in clinical oncology; potential and perspectives. June 30 2005. Rome 2005.
Tzankov A Eschwendtner A Augusti F Figl M Oberman EC Dimhofer S Went P. Diffuse large B-cell lymphoma with overexpression of cycline E substantives poor standard treatment response and interior outcome. Clin Cancer Res 2006; 12: 2125-32.
Dollad-Filhart M. Quantitative in situ analysis of βcatetin expression in breast cancer shows decreased expression is associated with poor prognosis. Cancer Res 2006; 66 (10): 5487-94.
Piccart-Gebhart MJ Procter M Leyland-Jones B Goldhirsch A Unteh M Smith I et al. Trastuzumab after adjuvant chemotherapy in her-2 positive breast cancer. New J Eng Med 2005; 353 (16): 1659-72.
Barrier A Van der Laan MJ. Colon cancer prognosis prediction by gene expression profiling. University of California Berkeley 2005 http://www.bepress.com/ucbbiostat/paper178,8/8/2006
Barenston RA Tenesa A Farrington SM et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med 2006; 354: 2751-63.
Baltić G Bogdanović G Baltić M Jurišić V Stojiljković B. Apoptoza i maligna transformacija ćelija - klinička iskustva. U: Apoptoza. Eksperimentalna i klinička iskustva. Novi Sad: SANU Ogranak u Novom Sadu; 2004. p. 81-97.
Waters JW Mc Leod HL. Cancer pharmacogenomics: current and future applications. BBA 2003; 1603 (2): 99-111.
Paik S Shak S Tang E et al. A mutagene assay to predict recurrence of tamoxifen treated node-negative breast cancer. N Engl J Med 2004; 351: 2817-26.
Nevins J. New genomic tests guide choice of chemotherapy in cancer patients. October 23 2006 http://www.Gammae.duke.edu/press/news10230.6,11/1/2006
Lan S Ling V. Application of pharmacogenoma for rational chemotherapy of lung cancers. http://www.genomicbe.ca/research-tech/research-projectshealth-lung-cancer.htm
Citin KV Albanasa L Fuji K et al. Application of expression genomic for predicting treatment response in cancer. Ann NY Acad Sci 2005; 1058: 186-95.
Ross MI. Early-stage melanoma: staging criteria and prognostic modeling. Clin Cancer Res 2006; 12: 2312s-2319s.
Wang X Li N Li H Liu B Qiu J Chen T Cao X. Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor alfa-induced apoptosis and cell growth arrest. Clin Cancer Res 2005; 11: 7545-53.
Kikucho T Diago Y Katagiri T Tsunoda T Okada K Kakiuchi S et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph node metastasis and sensitivity to anti-cancer drugs. Oncogene 2003; 22 (14): 2192-205.
Lu J Getz G Misaka GG Alvarez-Savedra E Lamb J Peck D et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834-8.
Meltzer PS. Cancer genomic: small RNAs with big impacts. Nature 2005; 435: 745-6.
Osada H Takashi T. MicroRNAs in biological processes and carcinogenesis. Cancerogenesis 2007; 28 (1): 2-12.
Zhang L Huang J Yang N Grwshock J Megraw MS Giannakakis A et al. MicroRNAs exhibit high frequency genomic alterations in human cancer. PNAS 2006; 103 (24); 9136-41.
Calin GA Croce CM. Micro RNA signatures in human cancers. Nature Rev Cancer 2006; 6: 857-66.
Volina S Calina GA Liu CG Ambs S Cimmno A Petrarcca P et al. A microRNA expression signature of human solid tumors defines cancer genes targets. PNAS 2006; 103 (7): 2257-61.
Nakajaima GO Hayashi K Xi Y Kudo K Uchiada K Takasaki K et al. Non-coding microRNAs has-let-7g and has-miR181b are associated with chemoresponse to S-1 in colon cancer. Cancer Genomics Proteomics 2006; 3: 317-24.
Rossi A Bonatti S Mallardo M Martinelli V Ciancia R Gravetti A et al. MicroRNAs: possible role in the molecular etiology of chronic myeloproliferative diseases. Haematology 2006; 91 (S3).
Tamaru Y Hyashizava Y. Cancer Research with noncoding RNA. Cancer Sci 2006; 97 (12): 1285-90.
Model F Ebert M De Vos T Tetzner R Schuster M Lesche R Sledziewski A Day RW. Detection of methylated DNA in plasma from colorectal cancer and controls by real-time PCR analysis. http://www.epigenomics.com
Koyanagi K Mori T O'Day SJ Martinez SR Wang HJ Hoon DSB. Association of circulating tumor cells with serum tumor related methylated DNA in peripheral blood of melanoma patients. Cancer Res 2006; 66 (12): 6111-7.
Ogino S Brahmandaw M Kawasaki T Kirkner GJ Loda M Fuchs CS. Epigenetic profiling of synchronous colorectal neoplasias by quantitative DNA methylation analysis. Modern Pathol 2006; 19 (8): 1083-90.
Roman-Gomez J Jimenez-Velasco A Agirre X Castillego JA Navaro G Calasanz MJ et al. CpG island methylator phenotype redefines the prognostic effect of t(12;21) in childhood acute lymphoblastic leukemia. Clin Cancer Res 2006; 12: 4845-50.
Livre A Blons H Houller AM. Clinicopathologic significance of mitochondrial D-loop mutation in head and neck carcinoma. Br J Cancer 2006; 94: 692-7.
Abu-Amero KK Alzahran AS Zou M Shi Y. Association of mitochondrial DNA transfersion mutations with medullary thyreoid carcinoma/multiple endocrine neoplasias type 2 syndrome. Oncogene 2006; 25: 677-84.
Meierhofer D Mayer JA Fink K Schmeller N Kofler B Sperl W. Mytochondrial DNA mutations in renal cell carcinomas reveal no general impact on energy metabolism. Br J Cancer 2006; 94: 268-74.
Giralda-Rosa W Vleuges RA Musiek A Sligh JE. High-throughput mitochondrial genome screening method for nonmelanoma skin cancer using multiplexed temperature gradient capillary electrophoresis. Clinical Chemistry 2005; 51: 305-11.
Jakupciak JP Wang WW Markowitz MF et al. Mitochondrial DNA as a cancer biomarker. JMD 2005; 7 (2): 97.
Parr RL Dakubo GD Crandall KA et al. Somatic mitochondrial DNA mutations in prostatic cancer and normal applying adjunct glands in comparison to agematched prostate samples without malignant histology. JMD2006; 8 (30): 312-19.
Parrallei P Xiao Y Fliss M et al. Detection of mtDNA mutations primary breast cancer and fine-needle aspirates. Cancer Res 2001; 61: 7623-6.