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

被引：363

作者：

Honeyman, Joshua N. ^{[1
,2
]}

Simon, Elana P. ^{[1
,3
]}

Robine, Nicolas ^{[4
]}

Chiaroni-Clarke, Rachel ^{[1
]}

Darcy, David G. ^{[1
,2
]}

Lim, Irene Isabel P. ^{[1
,2
]}

Gleason, Caroline E. ^{[1
]}

Murphy, Jennifer M. ^{[1
,2
]}

Rosenberg, Brad R. ^{[5
]}

Teegan, Lydia ^{[1
]}

Takacs, Constantin N. ^{[1
]}

Botero, Sergio ^{[1
]}

Belote, Rachel ^{[1
]}

Germer, Soren ^{[4
]}

Emde, Anne-Katrin ^{[4
]}

Vacic, Vladimir ^{[4
]}

Bhanot, Umesh ^{[6
]}

LaQuaglia, Michael P. ^{[2
]}

Simon, Sanford M. ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Cellular Biophys, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Surg, Div Pediat Surg, New York, NY 10065 USA

[3] Dalton Sch, New York, NY 10128 USA

[4] New York Genome Ctr, New York, NY 10013 USA

[5] Rockefeller Univ, Whitehead Presidential Fellows Program, New York, NY 10065 USA

[6] Mem Sloan Kettering Canc Ctr, Pathol Core Facil, New York, NY 10065 USA

来源：

SCIENCE | 2014年 / 343卷 / 6174期

关键词：

GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE; PAIRED-END; CLINICOPATHOLOGICAL FEATURES; BREAST-CANCER; LIVER; SURVIVAL; TUMOR; PHOSPHORYLATION; VARIANT;

D O I：

10.1126/science.1249484

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor affecting adolescents and young adults with no history of primary liver disease or cirrhosis. We identified a chimeric transcript that is expressed in FL-HCC but not in adjacent normal liver and that arises as the result of a similar to 400-kilobase deletion on chromosome 19. The chimeric RNA is predicted to code for a protein containing the amino-terminal domain of DNAJB1, a homolog of the molecular chaperone DNAJ, fused in frame with PRKACA, the catalytic domain of protein kinase A. Immunoprecipitation and Western blot analyses confirmed that the chimeric protein is expressed in tumor tissue, and a cell culture assay indicated that it retains kinase activity. Evidence supporting the presence of the DNAJB1-PRKACA chimeric transcript in 100% of the FL-HCCs examined (15/15) suggests that this genetic alteration contributes to tumor pathogenesis.

引用

页码：1010 / 1014

页数：5

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