In the era of targeted therapy, laboratory studies are an integral component of cancer clinical trials. Among the most powerful techniques connecting therapies and outcomes are assays which interrogate nucleic acid (DNA or RNA) using massively parallel sequencing (MPS). Nucleic acid-based approaches are implemented to detect either somatic sequence alterations ("mutations") compared to germline or structural variation including abnormal fusion of chromosomes, loss of normal DNA sequences ("deletions") or sequence duplications ("amplifications"). Alternatively, sequencing assays can target DNA from noncancerous cells to address different questions, including documenting the intact reference genome, genotyping of familial cancer syndromes, and genotyping of drug metabolizing enzymes of therapeutic importance. A highly targeted capture approach (using hundreds of pathway genes) is proposed in this proposal. UNC will provide high sample volume clinical sequencing in a regulatory compliant manner from day one of the grant. As a world leader in the production of human RNA-based cancer assays from both frozen and paraffin-embedded material, including microarrays, RNA sequencing, and targeted RNA quantification, assays are offered within a compliant setting. It is vital to provide expertise in the regulatory process to offer NGS assays prospectively for the purpose of treatment decision-making and patient randomization.
Aims 1 and 2 of this proposal involve providing an FDA- and CAP- compliant mechanism for high sample throughput RNA and DNA sequencing from frozen or paraffin-embedded samples provided from multi-institutional cooperative group clinical trials. RNA sequencing will be offered for 3 formats, RNA-Seq, NanoString, and G- rtPCR, to allow both comprehensive RNA sequencing and inexpensive targeted RNA profiling. DNA sequencing will be offered for both whole exome and targeted capture by next generation sequencing as well as quantitative DNA measures by NanoString.
The third aim i s to develop and provide a regulatory services core to expedite approval for both FDA and CLIA compliant assays designed to be implemented for prospective clinical trials.

Public Health Relevance

The adoption of genomic medicine in the clinic has incredible potential to clarify disease origins, improve diagnosis, and usher in the era of personalized medicine for cancer patients. In this proposal, we plan to provide methods and systems in association with clinical trials for tumor samples to be evaluated for specific changes that may be targeted in therapy.

National Institute of Health (NIH)
Cooperative Clinical Research--Cooperative Agreements (U10)
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Special Emphasis Panel (ZCA1)
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Mooney, Margaret M
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University of North Carolina Chapel Hill
Internal Medicine/Medicine
Schools of Medicine
Chapel Hill
United States
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