Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:020040 (SEPT3)
 17 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncogenic BRAF fusions have emerged as an alternate mechanism for BRAF activation in melanomas and other cancers. A number of BRAF fusions with different 5' gene partners and BRAF exon breakpoints have been described, but the effects of different partners and breakpoints on cancer phenotypes and treatment responses has not been well characterized. Targeted RNA sequencing was used to screen 60 melanoma patient-derived xenograft (PDX) models for BRAF fusions. We identified three unique BRAF fusions, including a novel SEPT3-BRAF fusion, occurring in four tumors (4/60, 6.7%), all of which were "pan-negative" (lacking other common mutations) (4/18, 22.2%). The BRAF fusion PDX models showed variable growth rates and responses to MAPK inhibitors in vivo. Overexpression of BRAF fusions identified in our study, as well as other BRAF fusions previously identified in melanomas, resulted in a high degree of variability in 2D proliferation and 3D invasion between the different fusions. While exogenously expressed BRAF fusions all responded to MAPK inhibition in vitro, we observed potential differences in signaling and feedback mechanisms. In summary, BRAF fusions are actionable therapeutic targets, however there are significant differences in phenotypes, treatment responses, and signaling which may be clinically relevant.
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PMID:BRAF fusions identified in melanomas have variable treatment responses and phenotypes. 3025 12

Septins are GTP-binding proteins that polymerize to form filaments involved in several important biological processes. In human, 13 distinct septins genes are classified in four groups. Filaments formed by septins are complex and usually involve members of each group in specific positions. Expression data from GTEx database, a publicly available expression database with thousands of samples derived from multiple human tissues, was used to evaluate the expression of septins. The brain is noticeably a hotspot for septin expression where few genes contribute to a large portion of septin transcript pool. Co-expression data between septins suggests two predominant specific complexes in brain tissues and one filament in other tissues. SEPT3 and SEPT5 are two genes highly expressed in the brain and with a strong co-expression in all brain tissues. Additional analysis shows that the expression of these two genes is highly variable between individuals, but significantly dependent on the individual's age. Age-dependent decrease of expression from those two septins involved in synapses reinforces their possible link with cognitive decay and neurodegenerative diseases associated with aging. Analysis of enrichment of Gene Ontology terms from lists of genes consistently co-expressed with septins suggests participation in diverse biological processes, pointing out some novel roles for septins. Interestingly, we observed strong consistency of some of these terms with experimentally described roles of septins. Coordination of septins expression with genes involved in DNA repair and cell cycle control may provide insights for previously described links between septins and cancer.
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PMID:A blueprint of septin expression in human tissues. 3108 37