Editors' ChoiceCancer

The Transcriptome Speaks

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Science Translational Medicine  25 May 2011:
Vol. 3, Issue 84, pp. 84ec76
DOI: 10.1126/scitranslmed.3002657

The ability to analyze all gene transcripts (RNA) within specific human tissues, known as the transcriptome, gives us an unprecedented global view of the molecular processes at play at any given time in a variety of physiologic and pathologic states. Novel insights into biological pathways for several cancers have been revealed using RNA sequencing technologies. Now, Kannan et al. demonstrate via transcriptome analysis that chimeric RNAs—the fusion of two gene transcripts—are enriched in human prostate cancer.

First, the authors sequenced the transcriptome of 20 cancer and 10 benign samples from patients with documented prostate adenocarcinoma. Nearly 1.3 billion transcripts were generated, and 2369 chimeric events were identified. Thirty-two chimeras were considered highly recurrent (present in >50% of cancer cases) and were significantly more abundant in the cancer cases versus control specimens. Notably, five of the 32 chimeras have been documented previously in prostate cancer, which validated their discovery approach. Next, the investigators replicated their initial results using additional human cancer and benign samples from patients as well as cancerous and normal prostate epithelium cell lines. They found that the parent genes of the chimeras were expressed in both cancer and normal samples, providing further proof that the chimeric events were selectively enriched in cancer, independent of the expression of the parent genes. Furthermore, a single chimera, TMEM79-SMG5, was found to be highly expressed in cancer samples and androgen-sensitive cell lines exclusively.

These data underscore the utility of transcriptome sequencing and the emerging importance of gene chimeras in cancer. It is possible that in the future, chimeric signatures could be used as predictive biomarkers in prostate and other cancers. However, prospective trials and functional studies should first be performed in order to further define the mechanistic, regulatory, and clinical roles of chimeric proteins in prostate cancer.

K. Kannan et al., Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing. Proc. Natl. Acad. Sci. U.S.A. 12 May 2011 (10.1073/pnas.1100489108). [Abstract]

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