Although great strides have characterized cancer research and molecular diagnostics during the past decade, much work remains to exploit basic science discoveries for direct patient benefit from this major investment in healthcare research in cancer prevention, detection and treatment. With a re-emphasis on application of basic science knowledge to cancer patient care, a new program coordinating discovery, validation and application in clinical settings was instituted, the NCI’s Early Detection Research Network (EDRN) (http://edrn.nci.nih.gov/openhouse/bvl/nist.html).

The NIST DNA Measurements Group is integrated into the EDRN network to provide: 1) technical support to reconfigure early detection cancer assays for high throughput and 2) analytical validation services for promising biomarkers and assay systems arising in discovery labs of the EDRN. A study of performance and validation of induced chromosome breaks as an index of lung cancer susceptibility has been completed and published. A second “pre-validation” focused on determining whether mutations or mt-DNA homoplasmy will serve as a predictive indicator of early lung cancer. This was the first of the NIST cancer detection assays to incorporate a robotics platform. In technology development work, a third project has moved the assay of human serum telomerase from gel format with radioisotopes to a non-radioactive fluorescent detection method based on capillary electrophoresis. In addition, telomerase assays have been modified to enable robotic processing of samples and micro-sample analysis of cancer cells in body fluids with quantitative bioimaging. Finally, in response to the need for a human serum standard among EDRN labs using SELDI technology for novel early cancer detection biomarker discovery, the Cancer Biomarkers laboratory has explored the use of NIST’s Standard Reference Material 1951a (SRM1951a) as a prototype human serum standard. In related cancer detection studies, the amplified HER2 gene and overexpressed protein are targets of a novel cellular-based SRM for use in treatment stratification of breast cancer patients. Efforts are underway to provide measurement and standards support for molecular diagnostic testing. Current programs focus on qualitative, quantitative, and sizing measurements needs.  Reference materials under development for the detection of mutations in the nuclear-encoded TP53 gene complement those developed for human mitochondrial DNA mutations (Barbara Levin).  A program is underway to determine measurements needs for nucleotide repeat disorders such as those found in Polycystic Kidney Disease. These programs focus on accurate amplification and size discrimination of repeat elements, as well as sequencing these difficult templates.

Personnel: