private industry to develop and provide diagnostic tests for more common forms of cancer, such as lung, breast, colonic, and various hematopoietic malignancies. However, there is a chance that tests for less common cancers will go undeveloped if research in these areas is not subsidized. Congress has recently recognized the need to support research and development of drugs aimed at treating uncommon diseases. By analogy, similar support might be required to enable and encourage the development of diagnostic tests for less common types of cancer.

Future Needs

For molecular oncology to come to full fruition, further advances in understanding of the molecular mechanisms of carcinogenesis are needed, particularly those involved in the more common tumors of man. Improved cytogenetic techniques for solid tumors and almost weekly announcements of new mutations in genes such as TP53, RB1, RAS, and MCC in a variety of solid tumors are evidence that many mutations of potential clinical relevance are going to be discovered soon.

To prove that these mutations are clinically useful, however, will not be easy. National or cooperative tumor banks will be essential to this end, because they will allow retrospective correlation of the presence of newly identified molecular lesions with disease outcome. The procurement service established by the National Institutes of Health, which is designed to provide specimens to appropriate researchers, should aid this purpose, and this activity should be expanded, optimally with some standardized procedures for tumor characterization and clinical follow-up. Single reference laboratories employing well-controlled and reproducible methods in multi-institutional studies should be utilized to increase the probability of finding significant associations.

Use of genetic analysis in clinical management of patients places a premium on testing accuracy and speed. Tests based on polymerase chain reaction (PCR) need to be standardized, and means of ensuring an acceptably low false-positive and false-negative test rate need to be developed. Southern blotting is often too slow to provide clinical guidance; increased automation is needed. Better means of preserving tissue for FISH (and possibly cytogenetics) during shipping or initial morphologic analysis would be helpful. It is also evident that many of the important lesions are likely to be point mutations occurring at scattered locations within proto-oncogenes and tumor suppressor genes. A variety of techniques have been developed to analyze these types of changes, but many are technically difficult and too time consuming for routine clinical use. Development of new technology to speed and simplify detection of point mutations and other small genetic changes within fairly large regions of DNA will greatly increase the number of tumors from which clinically relevant molecular data can be gathered.



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