DNA-Microarrays as Tools for the Identification of Tumor Specific Gene Expression Profiles: Applications in Tumor Biology, Diagnosis and Therapy

Zusammenfassung

DNA-Microarrays erlauben die Analyse des nahezu kompletten Genexpressionsprogrammes von Tumorproben und entsprechenden Vergleichsgeweben in jeweils einem einzigen Experiment. Hierdurch lässt sich eine große Probenzahl in relativ kurzer Zeit bearbeiten. Tumorspezifische Genexpressionsprofile können zur molekularen Klassifikation von Tumoren verwendet werden und bieten ein neues diagnostisches Hilfsmittel. Tumorspezifisch exprimierte Gene ermöglichen darüber hinaus Einblicke in die Biologie der Tumorzelle und können zur Entwicklung neuer Therapiestrategien beitragen. Die mit Hilfe von DNA-Microarrays generierten großen Datenmengen bieten jedoch auch neue Herausforderungen an die bioinformatische Datenauswertung und aufgrund noch unbefriedigender Zuverlässigkeit und Reproduzierbarkeit dieser Technologie ist der Einsatz komplementärer Methoden zur Verifizierung der gewonnenen Ergebnisse notwendig.

Abstract

DNA-microarrays allow the analysis of almost the complete gene expression program of tumor samples and normal control samples in a single experiment. This allows the processing of a large number of samples in a reasonable short time. Tumor specific gene expression profiles can be used for molecular tumor classification and as a new diagnostic tool. In addition, the identification of tumor specific genes can help to understand the biology of tumor cells and identified genes can be used for the development of new therapeutic strategies. However, the huge amount of data generated by DNA-microarrays creates new challenges for data analysis. In addition, accuracy and reproducibility of the available techniques require complementary methods for verification of DNA-microarray data.

DNA-Microarrays - Tumordiagnostik - Tumor(immun)therapie

DNA-Microarrays - tumor diagnosis - tumor (immuno)therapy

References

• 1 Agami R. RNAi and related mechanisms and their potential use for therapy.  Curr Opin Chem Biol.. 2002;  6 829-834
• 2 Beer D G, Kardia S L, Huang C C, Giordano T J, Levin A M, Misek D E, Lin L, Chen G, Gharib T G, Thomas D G, Lizyness M L, Kuick R, Hayasaka S, Taylor J M, Iannettoni M D, Orringer M B, Hanash S. Gene-expression profiles predict survival of patients with lung adenocarcinoma.  Nat Med.. 2002;  8 816-824
• 3 Dong Y, Zhang H, Hawthorn L, Ganther H E, Ip C. Delineation of the Molecular Basis for Selenium-induced Growth Arrest in Human Prostate Cancer Cells by Oligonucleotide Array.  Cancer Res.. 2003;  63 52-59
• 4 Eisen M, Spellman P T, Brown P O, Botstein D. Cluster analysis and display of genome-wide expression patterns.  Proc Natl Acad Sci USA.. 1998;  95 14 863-14 868
• 5 Euer N, Schwirzke M, Evtimova V, Burtscher H, Jarsch M, Tarin D, Weidle U H. Identification of genes associated with metastasis of mammary carcinoma in metastatic versus non-metastatic cell lines.  Anticancer Res.. 2002;  22 733-740
• 6 Evans S J, Datson N A, Kabbaj M, Thompson R C, Vreugdenhil E, de Kloet E R, Watson S J, Akil H. Evaluation of Affymetrix Gene Chip sensitivity in rat hippocampal tissue using SAGE analysis. Serial Analysis of Gene Expression.  Eur J Neurosci.. 2002;  16 409-413
• 7 Ishi M, Hashimoto S, Tsutsumi S, Wada Y, Matsushima K, Kodama T, Aburatani H. Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis.  Genomics. 2000;  68 136-143
• 8 Kashani-Sabet M. Ribozyme therapeutics.  J Investig Dermatol Symp Proc.. 2002;  7 76-78
• 9 Khan J, Wei J S, Ringner M, Saal L H, Ladanyi M, Westermann F, Berthold F, Schwab M, Antonescu C R, Peterson C, Meltzer P S. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks.  Nat Med.. 2001;  7 673-679
• 10 Kojima T, Asami S, Chin M, Yoshida Y, Mugishima H, Suzuki T. Detection of chimeric genes in Ewing’s sarcoma and its clinical applications.  Biol Pharm Bull.. 2002;  25 991-994
• 11 Liang D C, Shih L Y, Yang C P, Hung I J, Chen S H, Jaing T H, Liu H C, Chang W H. Multiplex RT-PCR assay for the detection of major fusion transcripts in Taiwanese children with B-lineage acute lymphoblastic leukemia.  Med Pediatr Oncol.. 2002;  39 12-17
• 12 Machiels J P, van Baren N, Marchand M. Peptide-based cancer vaccines.  Semin Oncol.. 2002;  29 494-502
• 13 Morris E C, Bendle G M, Stauss H J. Prospects for immunotherapy of malignant disease.  Clin Exp Immunol.. 2003;  131 1-7
• 14 Milenic D E. Monoclonal antibody-based therapy strategies: providing options for the cancer patient.  Curr Pharm Des. 2002;  8 (19) 1749-64
• 15 Oberbauer R. Not nonsense but antisense - applications of antisense oligonucleotides in different fields of medicine.  Wien Klin Wochenschr.. 1997;  109 40-46
• 16 Peter M, Gilbert E, Delattre O. A multiplex real-time pcr assay for the detection of gene fusions observed in solid tumors.  Lab Invest.. 2001;  81 905-912
• 17 Pindolia V K, Zarowitz B J. Imatinib mesylate, the first molecularly targeted gene suppressor.  Pharmacotherapy.. 2002;  22 1249-1265
• 18 Sadovnikova E, Parovichnikova E N, Savchenko V G, Zabotina T, Stauss H J. The CD68 protein as a potential target for leukaemia-reactive CTL.  Leukemia.. 2002;  16 2019-2026
• 19 Sawyers C L. Rational therapeutic intervention in cancer: kinases as drug targets.  Curr Opin Genet Dev.. 2002;  12 111-115
• 20 Schaefer K L, Wai D H, Poremba C, Korsching E, van Valen F, Ozaki T, Boecker W, Dockhorn-Dworniczak B. Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays.  Virchows Arch.. 2002;  440 476-484
• 21 Schuhmacher M, Kohlhuber F, Holzel M, Kaiser C, Burtscher H, Jarsch M, Bornkamm G W, Laux G, Polack A, Weidle U H, Eick D. The transcriptional program of a human B cell line in response to Myc.  Nucleic Acids Res.. 2001;  29 97-406
• 22 Shou J, Soriano R, Hayward S W, Cunha G R, Williams P M, Gao W Q. Expression profiling of a human cell line model of prostatic cancer reveals a direct involvement of interferon signaling in prostate tumor progression.  Proc Natl Acad Sci U S A.. 2002;  99 2830-2835
• 23 Staege M S, Lee S P, Frisan T, Mautner J, Scholz S, Pajic A, Rickinson A B, Masucci M G, Polack A, Bornkamm G W. MYC overexpression imposes a nonimmunogenic phenotype on Epstein-Barr virus-infected B cells.  Proc Natl Acad Sci U S A.. 2002;  99 4550-4555
• 24 Su A I, Cooke M P, Ching K A, Hakak Y, Walker J R, Wiltshire T, Orth A P, Vega R G, Sapinoso L M, Moqrich A, Patapoutian A, Hampton G M, Schultz P G, Hogenesch J B. Large-scale analysis of the human and mouse transcriptomes.  Proc Natl Acad Sci U S A.. 2002;  99 4465-4470
• 25 Tibshirani R, Hastie T, Narasimhan B, Chu G. Diagnosis of multiple cancer types by shrunken centroids of gene expression.  Proc Natl Acad Sci U S A.. 2002;  99 6567-6572
• 26 Tusher V G, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad.  Sci U S A.. 2001;  98 5116-5121
• 27 van de Vijver M J, He Y D, van’t Veer L J, Dai H, Hart A A, Voskuil D W, Schreiber G J, Peterse J L, Roberts C, Marton M J, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers E T, Friend S H, Bernards R. A gene-expression signature as a predictor of survival in breast cancer.  N Engl J Med.. 2002;  347 1999-2009
• 28 Wai D H, Schaefer K L, Schramm A, Korsching E, van Valen F, Ozaki T, Boecker W, Schweigerer L, Dockhorn-Dworniczak B, Poremba C. Expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays.  Int J Oncol.. 2002;  20 441-451
• 29 Weinschenk T, Gouttefangeas C, Schirle M, Obermayr F, Walter S, Schoor O, Kurek R, Loeser W, Bichler K H, Wernet D, Stevanovic S, Rammensee H G. Integrated functional genomics approach for the design of patient-individual antitumor vaccines.  Cancer Res.. 2002;  62 5818-5827
• 30 Yagyu R, Hamamoto R, Furukawa Y, Okabe H, Yamamura T, Nakamura Y. Isolation and characterization of a novel human gene, VANGL1, as a therapeutic target for hepatocellular carcinoma.  Int J Oncol.. 2002;  20 1173-1178
• 31 Yeoh E J, Ross M E, Shurtleff S A, Williams W K, Patel D, Mahfouz R, Behm F G, Raimondi S C, Relling M V, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui C H, Evans W E, Naeve C, Wong L, Downing J R. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.  Cancer Cell.. 2002;  1 133-143