Detection of a Recurrent DNAJB1-PRKACA Chimeric Transcript in Fibrolamellar Hepatocellular Carcinoma

Author:

Honeyman Joshua N.12,Simon Elana P.13,Robine Nicolas4,Chiaroni-Clarke Rachel1,Darcy David G.12,Lim Irene Isabel P.12,Gleason Caroline E.1,Murphy Jennifer M.12,Rosenberg Brad R.5,Teegan Lydia1,Takacs Constantin N.1,Botero Sergio1,Belote Rachel1,Germer Soren4,Emde Anne-Katrin4,Vacic Vladimir4,Bhanot Umesh6,LaQuaglia Michael P.2,Simon Sanford M.1

Affiliation:

1. Laboratory of Cellular Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

2. Division of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

3. The Dalton School, 108 East 89th Street, New York, NY 10128, USA.

4. New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA.

5. Whitehead Presidential Fellows Program, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

6. Pathology Core Facility Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Abstract

Oncogenic Suspect Exposed It can be difficult logistically to study the genomics of rare variants of common cancers. Nevertheless, Honeyman et al. (p. 1010 ) 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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