Genomic Fabric Remodeling in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC): A New Paradigm and Proposal for a Personalized Gene Therapy Approach

摘要

We applied the genomic fabric principles for personalized gene therapy to a case of clear cell renal cell carcinoma (ccRCC). Despite decades of research, the process of finding the molecular mechanisms responsible for the disease and, more importantly, the therapeutic solution is still a work in progress. We analyzed the transcriptomes of the chest wall metastasis, two distinct cancer nodules, and the cancer-free surrounding tissue in the surgically removed right kidney of a Fuhrman grade 3 metastatic ccRCC patient. The studies revealed that even histopathologically equally classified cancer nodules from the same kidney have different transcriptomic topologies, requiring tailored therapeutic solutions not only for each patient but even for each cancer nodule. We identified death-associated protein kinase 3 (DAPK3); transcription activation suppressor (TASOR); family with sequence similarity 27, member C, long non-coding RNA (FAM27C); and UDP-N-acetylglucosaminyltransferase subunit (ALG13) as the gene master regulators of the four profiled regions and proposed molecular mechanisms by which expression manipulation of TASOR and ALG13 may selectively destroy the cancer cells without affecting many of the normal cells.