Editors' ChoiceCancer

Oncogenic Suspect Exposed

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Science Signaling  04 Mar 2014:
Vol. 7, Issue 315, pp. ec62
DOI: 10.1126/scisignal.2005228

It can be difficult logistically to study the genomics of rare variants of common cancers. Nevertheless, Honeyman et al. studied fibrolamellar hepatocellular carcinoma (FL-HCC), a rare and poorly understood liver tumor that affects adolescents and young adults and for which there is no effective treatment. FL-HCCs from 15 patients all expressed a chimeric RNA transcript and protein containing sequences from a molecular chaperone fused in frame with sequences from the catalytic domain of protein kinase A. The chimeric protein retained kinase activity in vitro. Such recurrent gene fusions in cancer may signal a role in pathogenesis and provide an opportunity for therapeutic intervention.

J. N. Honeyman, E. P. Simon, N. Robine, R. Chiaroni-Clarke, D. G. Darcy, I. I. P. Lim, C. E. Gleason, J. M. Murphy, B. R. Rosenberg, L. Teegan, C. N. Takacs, S. Botero, R. Belote, S. Germer, A.-K. Emde, V. Vacic, U. Bhanot, M. P. LaQuaglia, S. M. Simon, Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science 343, 1010–1014 (2014). [Abstract] [Full Text]

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