In the current era of Precision Medicine, laboratory studies are an integral component of cancer clinical trials. Amongst the most powerful techniques connecting therapies to specific patients are assays that interrogate nucleic acids (DNAseq and/or RNAseq), which are now most typically done using massively parallel sequencing (MPS). RNAseq now offers an extremely powerful approach for querying the tumor genome, where gene expression profiles have proven value in providing prognostic information, predictive information, and also critical information on the tumor microenvironment including quantitative measures of immune infiltrations. In addition, DNA based approaches can also be clinically informative in detecting somatic sequence alterations (mutations), structural variations (fusions), loss of normal DNA sequences (deletions), or sequence gains (amplifications). Alternatively, sequencing assays can target DNA from noncancerous cells to address additional questions including identification of familial predisposition, and genotyping of drug metabolizing enzymes of therapeutic importance. Through this Project, the UNC / UTHSC UNITS team will provide high volume clinical grade sequencing in a regulatory compliant manner from day one of the grant. As a world leader in the production of human RNA- based cancer data, from both frozen and FFPE, including RNA sequencing and targeted RNA quantification, RNA-based assays are offered within a compliant setting. We are also highly experienced with common, and complex, DNA-based assays and offer these as well. Aims 1 and 2 of this proposal involve providing an FDA- and CAP- compliant mechanism for high sample throughput for RNA- and DNA-sequencing from samples provided from multi-institutional cooperative group trials. RNA sequencing will be offered in 3 formats, RNA- Seq, NanoString, and Q-rt-PCR, to allow both comprehensive coverage and inexpensive targeted RNA profiling. DNA sequencing will be offered for both whole exome and targeted capture by MPS, as well as quantitative DNA measures by NanoString. The third aim is to develop and provide data sharing formats and an infrastructure for the proper dissemination of clinical trial sequence-based patient information, which is needed is this era of Big Data.

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, know how, and robust technologies, in association with clinical trial specimens, for tumor samples to be evaluated for genomic changes that may be targeted by molecular-based therapies.