sequence tags that allows efficient selection of new potential tumor-associated genes. The resulting ranked list of candidates is analyzed in terms of its content in known genes, used as controls, and the new candidates are further tested for selective expression in normal and tumor tissues by real-time polymerase chain reaction with reverse transcription. The most highly tumor-specific candidates are then pursued to full-length cloning. We present the discovery of a series of new genes that are upregulated in colon cancer.

Gene expression profiling through the use of nucleic acid arrays is a powerful method for the molecular classification of human neoplasms. Laser capture microdissection is an equally useful technique to selectively isolate defined cell populations from heterogeneous histological tissue sections. In this report, we demonstrate how a modest use of laser capture microdissection is sufficient to isolate nanogram quantities of high-quality RNA. Together with the use of several internal standards and microcapillary electrophoresis of input RNA, two rounds of linear molecular amplification have been used to generate sufficient quantities of labeled target for hybridization to high-density oligonucleotide expression arrays. Results demonstrate that the technique is reproducible, generates only modest biasing of the original transcript population, and is comparable to the sensitivity achieved with standard methodology. Using this approach, we have compared the expression profiles of nonmalignant human breast epithelium and adjacent ductal carcinoma in situ lesions from breast cancer patients. Several genes, previously implicated in human breast cancer progression, demonstrate differential expression among the microdissected cell populations. (Am J Pathol

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Biorepositories offer tremendous scientific value to a wide variety of customer groups (academic, commercial, industrial) in their ability to deliver a centralized, standardized service model, encompassing both biospecimen storage and related laboratory services. Generally, the scientific expertise and economies of scale that are offered in centralized, properly resourced research biobanks has yielded value that has been well-recognized by universities, pharmaceutical companies, and other sponsoring institutions. However, like many facets of the economy, biobanks have been under increasing cost pressure in recent years. This has been a particular problem in the academic arena, where direct support from grant sources (both governmental and philanthropic) typically now is more difficult to secure, or provides reduced financial support, relative to previous years. One way to address this challenge is to establish or enhance a well-defined fee-for-service model which is properly calibrated to cover operational costs while still offering competitive value to users. In this model, customers are never charged for the biospecimens themselves, but rather for the laboratory services associated with them. Good communication practices, proper assessment of value, implementation of best practices, and a sound business plan are all needed for this initiative to succeed. Here we summarize our experiences at Washington University School of Medicine in the expectation they will be useful to others.

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