| http://purl.uniprot.org/citations/27324824 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27324824 | http://www.w3.org/2000/01/rdf-schema#comment | "Histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are not commonly used in clinical practice for treatment of B-cell lymphomas, although a subset of patients with refractory or relapsed B-cell lymphoma achieved partial or complete remissions. Therefore, the purpose of this study was to identify molecular features that predict the response of B-cell lymphomas to SAHA treatment. We designed an integrative approach combining drug efficacy testing with exome and captured target analysis (DETECT). In this study, we tested SAHA sensitivity in 26 B-cell lymphoma cell lines and determined SAHA-interacting proteins in SAHA resistant and sensitive cell lines employing a SAHA capture compound (CC) and mass spectrometry (CCMS). In addition, we performed exome mutation analysis. Candidate validation was done by expression analysis and knock-out experiments. An integrated network analysis revealed that the Src tyrosine kinase Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog (FGR) is associated with SAHA resistance. FGR was specifically captured by the SAHA-CC in resistant cells. In line with this observation, we found that FGR expression was significantly higher in SAHA resistant cell lines. As functional proof, CRISPR/Cas9 mediated FGR knock-out in resistant cells increased SAHA sensitivity. In silico analysis of B-cell lymphoma samples (n = 1200) showed a wide range of FGR expression indicating that FGR expression might help to stratify patients, which clinically benefit from SAHA therapy. In conclusion, our comprehensive analysis of SAHA-interacting proteins highlights FGR as a factor involved in SAHA resistance in B-cell lymphoma."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.molonc.2016.06.001"xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Chen C."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Fischer U."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Munk C."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Hummel M."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Schmidt D."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Borkhardt A."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Hirsch B."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Seitz V."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Hain A."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Joosten M."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Ginzel S."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Gombert M."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Dreger M."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Sommerfeld A."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Blex C."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Koster H."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Linka R.M."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Baldus C.D."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Seegebarth A."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Thiele R."xsd:string |
| http://purl.uniprot.org/citations/27324824 | http://purl.uniprot.org/core/author | "Dieks H."xsd:string |