Discipline: Biological Sciences
Subcategory: Cancer Research
Skylar Groves - Norfolk State University
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. It accounts for 3-5% of newly diagnosed cancer cases in the United States. In advanced ccRCC cases, there can be a direct extension of the cancer into the renal vein and inferior vena cava (IVC). The comprehensive molecular profile of ccRCC with IVC thrombus is unknown. Hence, it is unclear if a single biopsy of the kidney tumor is representative of the molecular alterations in the tumor thrombus. We retrospectively identified patients with ccRCC and IVC thrombus who underwent surgical removal. Formalin-fixed paraffin-embedded (FFPE) specimens were retrieved and H & E stains were re-reviewed by a genitourinary pathologist to identify areas for multi-region analyses of the primary tumor and the IVC thrombus. Punch biopsies of these regions were performed, DNA and RNA were co-isolated from each sample and subjected to targeted next generation sequencing (NGS). The molecular profile of the primary tumor regions were then compared with those of the matched tumor thrombi to determine if a single biopsy core can capture the overall genomic landscape of ccRCC and to identify any specific alterations associated with tumor thrombus formation. We identified 5 patients with ccRCC with associated IVC tumor thrombus and 1 patient with ccRCC with both tumor thrombus, IVC wall invasion. Targeted DNA sequencing using a custom, targeted, pan-genitourinary cancers sequencing panel was performed on 26 samples from all 5 patients. We identified high confidence somatic mutations using our in house bioinformatics analyses pipelines. We observed significant heterogeneity in the molecular profile of the primary tumor versus the matched tumor thrombus. RNA NGS is currently ongoing to identify differential expression changes between the primary ccRCC and IVC thrombi. Our data suggest that the molecular profile of a single biopsy core does not capture the molecular heterogeneity in primary ccRCC as well as the concomitant IVC thrombus. Additional studies are needed to understand the prognostic significance of this heterogeneity and develop novel molecular diagnostic tests to overcome tumor heterogeneity.
Funder Acknowledgement(s): N/A
Faculty Advisor: Simpa S. Salami, Simpa@med.umich.edu
Role: I participated in the DNA and RNA extraction process. We lysed the cells, separated the DNA and RNA, and purified each genetic component. Then, through PCR, we amplified targeted sequences to prepare them for Ion Torrent Next Generation Sequencing to compare the DNA and RNA makeup of our samples.