Cancer Cell microarray
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Cancer Microarray Rationale
• One sequence variation or polymorphism every 1000 bp • 3% of our genome codes for proteins, we have 90 000 coding variants, many of these might be silent • The majority of mutation discovered in ~ 50 cancer genes • There are more than 200 different types of cancer • A few hundred genes are frequently mutated in cancer • Many genes have the potential to be mutated at one of many location • Each and every tumor is unique
Cancer Cell Lines Source
• American Type Culture Collection (ATCC)’s Cell Biology Collection is the most comprehensive and diverse of its kind in the world consisting of over 4,000 cell lines from over 150 different species. • It holds over 950 cancer cell lines (including 700 human cancer cell lines)
Cancer Cell Line Microarray Rationale
• Cell lines derived from human tumours have been extensively used as experimental models of neoplastic disease • The inaccessibility of human tumours and normal tissue makes it likely that such cell lines will continue to be used as experimental models for the foreseeable future • Newly available genomics tools allowed us to explore variation in gene expression on a genomic scale • Cancer cell lines maintain the gene-expression pattern established during differentiation in vivo, with subtle adaptations to cope with the cell-culture environment • Cell lines can help to elucidate the dysfunctional nature of tumor cells but the data must be maintained in the correct context
Cancer Cell Microarray Application
• DNA Chip and Tissue Chip have the potential to provide 10 - 100 times more data than conventional means • Used to identify a handful of critical genes that will lead to a more-detailed taxonomy of tumors • DNA Chip could be considered as a fishing exercise to identify a handful of genes that have a diagnostic potential, Cancer Cell Chip could be used to confirm the diagnostic potential • DNA Chip and Cancer Cell Microarray provided a novel means to identify the prominent features in the gene expression patterns that appeared to reflect 'molecular signatures' of the tissue from which the cells originated
Cancer Cell Microarray Application
• DNA Chip and Cancer Cell Microarray provided a novel molecular characterization of human cancer cell lines and their relationships to tumours in vivo • Cance Cell Microarray assays can measure the transcriptional effects of changes in gene function under different conditions • They can reveal genes that characterize tissue type, developmental stage, or responses to environmental conditions or genetic modifications. • Cance Cell Microarray assays will therefore become a general feature of experimental protocols in genetics and cell physiology • Cance Cell Microarray can be used to predict clinical outcome
– – – – Gene expression patterns related to the histologic origins of the cell lines Physiological variation reflected in gene expression patterns Cell lines facilitate interpretation of gene expression patterns in complex clinical samples Specific features of the gene expression patterns related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response – Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue.
Cancer Cell Line Microarray Rationale
• The NCI’s studies of 60 cancer cell lines derived from tumours from a variety of tissues and organs using cDNA microarrays of 8,000 unique genes indicated :
Cancer Cell Lines Types
• Adenocarcinoma, Burkitt’s lymphoma, Colorectal carcinoma, ductal carcinoma, Epidermoid carcinoma, Ewing’s sarcoma, Fibrosarcoma, Gastric carcinoma, Giant cell sarcoma, Hepatocellular carcinoma, Hodgkin’s disease, lymphoma, Malignant melanoma, Neuroblastoma, Osteocarcinoma, Plasmacytoma, Rhabdomyosarcoma, squamous cell carcinoma, Transitional cell carcinoma, Uterine sarcoma……..
Uses in Molecular Pharmacology
• To study the pharmacological implications of gene-expression profiling on cancer cells • The gene expression patterns are compared in untreated and treated cells, the data relates to sensitivity to drugs and to the molecular consequences of therapy • To understand molecular pharmacology • To aid in the process of drug discovery • To provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour • DNA Chip and Tissue Chip are used to explore a large set of possible genegene, gene-drug and drug-drug relationships simultaneously • It is possible to assess differences among cells at the DNA and protein levels as well
wenku.baidu.com
Cancer Cell Lines Source • European Collection of Cell Cultures • Japanese Cancer Research Resources Bank • The University of Michigan Breast Cell Line/Tissue Bank and Data Base • The National Laboratory for the Genetics of Israeli Populations • Chinese Collection of Cell Cultures (CCCC) ? • Other academic and clinic labs
• One sequence variation or polymorphism every 1000 bp • 3% of our genome codes for proteins, we have 90 000 coding variants, many of these might be silent • The majority of mutation discovered in ~ 50 cancer genes • There are more than 200 different types of cancer • A few hundred genes are frequently mutated in cancer • Many genes have the potential to be mutated at one of many location • Each and every tumor is unique
Cancer Cell Lines Source
• American Type Culture Collection (ATCC)’s Cell Biology Collection is the most comprehensive and diverse of its kind in the world consisting of over 4,000 cell lines from over 150 different species. • It holds over 950 cancer cell lines (including 700 human cancer cell lines)
Cancer Cell Line Microarray Rationale
• Cell lines derived from human tumours have been extensively used as experimental models of neoplastic disease • The inaccessibility of human tumours and normal tissue makes it likely that such cell lines will continue to be used as experimental models for the foreseeable future • Newly available genomics tools allowed us to explore variation in gene expression on a genomic scale • Cancer cell lines maintain the gene-expression pattern established during differentiation in vivo, with subtle adaptations to cope with the cell-culture environment • Cell lines can help to elucidate the dysfunctional nature of tumor cells but the data must be maintained in the correct context
Cancer Cell Microarray Application
• DNA Chip and Tissue Chip have the potential to provide 10 - 100 times more data than conventional means • Used to identify a handful of critical genes that will lead to a more-detailed taxonomy of tumors • DNA Chip could be considered as a fishing exercise to identify a handful of genes that have a diagnostic potential, Cancer Cell Chip could be used to confirm the diagnostic potential • DNA Chip and Cancer Cell Microarray provided a novel means to identify the prominent features in the gene expression patterns that appeared to reflect 'molecular signatures' of the tissue from which the cells originated
Cancer Cell Microarray Application
• DNA Chip and Cancer Cell Microarray provided a novel molecular characterization of human cancer cell lines and their relationships to tumours in vivo • Cance Cell Microarray assays can measure the transcriptional effects of changes in gene function under different conditions • They can reveal genes that characterize tissue type, developmental stage, or responses to environmental conditions or genetic modifications. • Cance Cell Microarray assays will therefore become a general feature of experimental protocols in genetics and cell physiology • Cance Cell Microarray can be used to predict clinical outcome
– – – – Gene expression patterns related to the histologic origins of the cell lines Physiological variation reflected in gene expression patterns Cell lines facilitate interpretation of gene expression patterns in complex clinical samples Specific features of the gene expression patterns related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response – Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue.
Cancer Cell Line Microarray Rationale
• The NCI’s studies of 60 cancer cell lines derived from tumours from a variety of tissues and organs using cDNA microarrays of 8,000 unique genes indicated :
Cancer Cell Lines Types
• Adenocarcinoma, Burkitt’s lymphoma, Colorectal carcinoma, ductal carcinoma, Epidermoid carcinoma, Ewing’s sarcoma, Fibrosarcoma, Gastric carcinoma, Giant cell sarcoma, Hepatocellular carcinoma, Hodgkin’s disease, lymphoma, Malignant melanoma, Neuroblastoma, Osteocarcinoma, Plasmacytoma, Rhabdomyosarcoma, squamous cell carcinoma, Transitional cell carcinoma, Uterine sarcoma……..
Uses in Molecular Pharmacology
• To study the pharmacological implications of gene-expression profiling on cancer cells • The gene expression patterns are compared in untreated and treated cells, the data relates to sensitivity to drugs and to the molecular consequences of therapy • To understand molecular pharmacology • To aid in the process of drug discovery • To provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour • DNA Chip and Tissue Chip are used to explore a large set of possible genegene, gene-drug and drug-drug relationships simultaneously • It is possible to assess differences among cells at the DNA and protein levels as well
wenku.baidu.com
Cancer Cell Lines Source • European Collection of Cell Cultures • Japanese Cancer Research Resources Bank • The University of Michigan Breast Cell Line/Tissue Bank and Data Base • The National Laboratory for the Genetics of Israeli Populations • Chinese Collection of Cell Cultures (CCCC) ? • Other academic and clinic labs