Ontogeny and oncogenesis balance the transcriptional profile of renal cell cancer

Ena Wang, Rudolf Lichtenfels, Jurgen Bükur, Yvonne Ngalame, Monica C. Panelli, Barbara Seliger, Francesco M. Marincola

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28 Citations (Scopus)

Abstract

Global transcript analysis is increasingly used to describe cancer taxonomies beyond the microscopic reach of the eye. Diagnostic and prognostic portraits are formulated by ranking cancers according to transcriptional proximity. However, the role that distinct biological factors play in defining these portraits remains undefined. It is likely that the transcriptional repertoire of cancers depends, on one hand, on the anamnestic retention of their ontogenesis and, on the other, on the emergence of novel expression patterns related to oncogenesis. We compared the transcriptional profile of primary renal cell cancers (RCCs) with that of normal kidney tissue and several epithelial cancers of nonrenal origin to weigh the contribution that ontogeny and oncogenesis make in molding their genetic profile. Unsupervised global transcript analysis demonstrated that RCCs retain transcriptional signatures related to their ontogeny and cluster close to normal renal epithelium. When renal lineage-associated genes are removed from the analysis and cancer-specific genes are analyzed, RCCs segregate with other cancers with limited lineage specificity underlying a predominance of the oncogenic process over lineage specificity. However, a RCC-specific set of oncogenesis-related genes was identified and surprisingly shared by sarcomas. In summary, the transcriptional portrait of primary RCCs is largely dominated by ontogeny. Genes responsible for lineage specificity may represent poor molecular targets for immune or drug therapy. Most genes associated with oncogenesis are shared with other cancers and may represent better therapeutic targets. Finally, a small subset of genes is associated with lineage-specific oncogenesis, and these may provide information regarding the biological behavior of RCCs and facilitate diagnostic classification of RCCs.

Original languageEnglish
Pages (from-to)7279-7287
Number of pages9
JournalCancer Research
Volume64
Issue number20
DOIs
Publication statusPublished - 15 Oct 2004

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wang, E., Lichtenfels, R., Bükur, J., Ngalame, Y., Panelli, M. C., Seliger, B., & Marincola, F. M. (2004). Ontogeny and oncogenesis balance the transcriptional profile of renal cell cancer. Cancer Research, 64(20), 7279-7287. https://doi.org/10.1158/0008-5472.CAN-04-1597