DNA technology, the clinical laboratory, and the future

Objective.-To review the advances in clinically useful molecular biological techniques and their applications in clinical practice as presented at the Ninth Annual William Beaumont Hospital DNA Symposium. Data Sources-The 10 manuscripts submitted were reviewed and their major fin dings were compared with literature on the same topic. Study Selection.-One manuscript reviewed the development of pharmacogenetic s, 3 described analytic approaches to detect aneuploidy or cancer, 1 descri bed transcription factor E2F-1 increase during apoptosis, 2 reported on gen etic and pharmacologic factors that influence platelet aggregation, 2 descr ibed molecular methods for detecting long QT syndrome or mycobacteria, and 1 reported a modification in collection of buccal DNA. Data Synthesis.-Genomic and proteomic approaches to develop clinically usef ul assays have been successful. Aneuploidy can be easily detected by compar ative genomic hybridization, which does not require cell culture like cytog enetics. Mutations have been characterized for a variety of hereditary canc er syndromes, 2 inherited long QT syndromes, and thromboembolism. P\(A1) an d P\(A2) polymorphisms in platelets are associated with a difference in agg regation inhibition by estrogen, another example of genotypic pharmacogenet ics. Protein expression differences may define colorectal cancer stage and explain apoptotic signal transduction. Mycobacterial detection by nucleic a cid amplification and simplified buccal DNA collection demonstrate cost-eff ective strategies. Concluion.-The working draft of the Human Genome Project is completed and t he number of clinically useful molecular pathologic techniques and assays w ill expand as additional disease-associated mutations are defined. Expanded use of database software for genomic and proteomic screening should increa se the efficiency of clinical useful assay development.