Traditionally, tumours have been categorized on the basis of histology. However, the staining pattern of cancer cells viewed under the microscope is insufficient to reflect the complicated underlying molecular events that drive the neoplastic process. By surveying thousands of genes at once, using DNA arrays, it is now possible to read the molecular signature of an individual patient's tumour. When the signature is analysed with clustering algorithms, new classes of cancer emerge that transcend distinctions based on histological appearance alone. Using DNA arrays, protein arrays and appropriate experimental models, the ultimate goal is to move beyond correlation and classification to achieve new insights into disease mechanisms and treatment targets.
Key Points
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Traditional approaches to cancer classification and diagnosis have been based on histological examination.
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Extensive genome data and DNA array technology have provided opportunities to monitor gene expression in cancer cells for thousands of genes at once.
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When preparing tissue samples, tissue fixation procedures must allow preservation of macromolecules.
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Tissue heterogeneity is another important issue for research on cancerous cells. Approaches to tissue heterogeneity include global sampling, the use of cell lines derived from tumours, and laser capture microdissection. Several studies have reported transcriptional profiling of cancer using DNA arrays. These studies have uncovered classes of cancer that extend traditional classification on the basis of histology and morphology.
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Clustering of genes by transcriptional profiling is also providing insights into gene function and cancer pathology, such as metastasis.
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Technologies are being developed that will allow cellular protein and signal pathway profiling. This will further extend our understanding of the molecular pathology of cancer, and can lead to patient-tailored therapies.
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Glossary
- CARCINOMA
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Cancer originating from epithelial cells. Most human cancers that are not leukaemias or lymphomas are carcinomas.
- SERUM MARKERS
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Substances that are soluble in the serum (non-cellular portion of blood) and that are present at high levels in association with specific cancers.
- STROMAL CELLS
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Connective tissue cells such as fibroblasts.
- CARCINOMA IN SITU
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An early non-invasive form of carcinoma, confined to the epithelium.
- LEUKAEMIA
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A malignant disorder in which precursors of white blood cells proliferate and accumulate.
- LYMPHOMA
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A cancer of lymphoid cells, producing a distinct tumour mass. The many different types of lymphoma are thought to arise from different subtypes of immune defence cells.
- GERMINAL CENTRES
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Subregions of lymph nodes rich in B cells, which are formed or expand during the activation and differentiation of B cells.
- ELISA
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A sensitive antibody-based method for the detection of an antigen such as a protein.
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Liotta, L., Petricoin, E. Molecular profiling of human cancer. Nat Rev Genet 1, 48–56 (2000). https://doi.org/10.1038/35049567
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DOI: https://doi.org/10.1038/35049567
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