Aberrations of protein-coding genes are a focus of cancer genomics; however, the impact of oncogenes on expression of the ~50% of transcripts without protein-coding potential, including long noncoding RNAs (lncRNAs), has been largely uncharacterized. Activating mutations in the BRAF oncogene are present in >70% of melanomas, 90% of which produce active mutant BRAF(V600E) protein. To define the impacts of oncogenic BRAF on the melanocyte transcriptome, massively parallel cDNA sequencing (RNA-seq) was performed on genetically matched normal human melanocytes with and without BRAF(V600E) expression. To enhance potential disease relevance by verifying expression of altered genes in BRAF-driven cancer tissue, parallel RNA-seq was also undertaken of two BRAF(V600E)-mutant human melanomas. BRAF(V600E) regulated expression of 1027 protein-coding transcripts and 39 annotated lncRNAs, as well as 70 unannotated, potentially novel, intergenic transcripts. These transcripts display both tissue-specific and multi-tissue expression profiles and harbor distinctive regulatory chromatin marks and transcription factor binding sites indicative of active transcription. Coding potential analysis of the 70 unannotated transcripts suggested that most may represent newly identified lncRNAs. BRAF-regulated lncRNA 1 (BANCR) was identified as a recurrently overexpressed, previously unannotated 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. BANCR knockdown reduced melanoma cell migration, and this could be rescued by the chemokine CXCL11. Combining RNA-seq of oncogene-expressing normal cells with RNA-seq of their corresponding human cancers may represent a useful approach to discover new oncogene-regulated RNA transcripts of potential clinical relevance in cancer.
Citation Format: Ross J. Flockhart, Dan E. Webster, Kun Qu, Nicholas Mascarenhas, Joanna Kovalski, Markus Kretz, Khavari A. Paul. BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-248. doi:10.1158/1538-7445.AM2013-LB-248
We describe the technical details and the performance of a large array which detects both the electron and muon components in extensive air showers with energies >_ 10 14 eV. The array was designed to search for-y-rays from astrophysical sources. The background of cosmic rays is reduced by the selection of moon poor events. The array consists of 1089 scintillation detectors on the surface covering an area of 0.23 km 2 and 1024 scintillation counters of 2.5 m2 each, buried 3 m below the surface for muon detection. Each of the surface detectors has its own local electronics and local data storage controlled by a microprocessor. The array is located at Dugway, Utah USA (40.2°N, 112.8°W) where the average atmospheric depth is 870 g/cm 2.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.