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.
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.
|Patel, Nirali M; Michelini, Vanessa V; Snell, Jeff M et al. (2018) Enhancing Next-Generation Sequencing-Guided Cancer Care Through Cognitive Computing. Oncologist 23:179-185|
|George, Julie; Walter, Vonn; Peifer, Martin et al. (2018) Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat Commun 9:1048|
|Walter, Vonn; Du, Ying; Danilova, Ludmila et al. (2018) MVisAGe Identifies Concordant and Discordant Genomic Alterations of Driver Genes in Squamous Tumors. Cancer Res 78:3375-3385|
|Sun, Wei; Bunn, Paul; Jin, Chong et al. (2018) The association between copy number aberration, DNA methylation and gene expression in tumor samples. Nucleic Acids Res 46:3009-3018|
|Kimes, Patrick K; Liu, Yufeng; Neil Hayes, David et al. (2017) Statistical significance for hierarchical clustering. Biometrics 73:811-821|
|Treece, Amanda L; Montgomery, Nathan D; Patel, Nirali M et al. (2016) FNA smears as a potential source of DNA for targeted next-generation sequencing of lung adenocarcinomas. Cancer Cytopathol 124:406-14|
|Montgomery, Nathan D; Parker, Joel S; Eberhard, David A et al. (2016) Identification of Human Papillomavirus Infection in Cancer Tissue by Targeted Next-generation Sequencing. Appl Immunohistochem Mol Morphol 24:490-5|
|Treece, Amanda L; Duncan, Daniel L; Tang, Weihua et al. (2016) Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns. Lab Invest 96:661-71|
|Hayes, D Neil; Van Waes, Carter; Seiwert, Tanguy Y (2015) Genetic Landscape of Human Papillomavirus-Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors. J Clin Oncol 33:3227-34|
|Hayes, D Neil; Kim, William Y (2015) The next steps in next-gen sequencing of cancer genomes. J Clin Invest 125:462-8|
Showing the most recent 10 out of 11 publications