Identification of the BRAF V600E mutation in a patient with sclerosing pneumocytoma: A case report
Authors: Jiang, Guanming; Zhang, Min; Tan, Qinquan; Lin, Shunhuan; Zeng, Yihong; Liu, Chun; Chen, Rongrong; Zhou, Jianping
Objectives: Sclerosing pneumocytoma (sclerosing hemangioma, SP) is a rare benign tumor of the lung with a low risk of recurrence. The genomic profile of SP is not well-known. Here we report gene mutation findings in a 17year-old girl with SP. Materials and methods: Immunohistochemistry (IHC), next-generation sequencing (NGS), and sanger sequencing were performed on the tumor tissue of this patient for pathological diagnosis and gene mutation analysis. Results and conclusion: Two mutations were identified in the tumor tissue by NGS and sanger sequencing: AKT1 E17K and BRAF (B-Raf proto-oncogene, serine/threonine kinase) V600E. This is the first case report of a BRAF V600E mutation in a patient with SP. This discovery extends our understanding of the pathogenesis of SP, and suggests the need for future testing of BRAF V600E in this rare tumor type.
KLF4 Acts as a wt-CFTR Suppressor through an AKT-Mediated Pathway
Authors: Sousa, Luis; Pankonien, Ines; Clarke, Luka A.; Silva, Iris; Kunzelmann, Karl; Amaral, Margarida D.
Cystic Fibrosis (CF) is caused by >2000 mutations in the CF transmembrane conductance regulator (CFTR) gene, but one mutation-F508del-occurs in similar to 80% of patients worldwide. Besides its main function as an anion channel, the CFTR protein has been implicated in epithelial differentiation, tissue regeneration, and, when dysfunctional, cancer. However, the mechanisms that regulate such relationships are not fully elucidated. Kruppel-like factors (KLFs) are a family of transcription factors (TFs) playing central roles in development, stem cell differentiation, and proliferation. Herein, we hypothesized that these TFs might have an impact on CFTR expression and function, being its missing link to differentiation. Our results indicate that KLF4 (but not KLF2 nor KLF5) is upregulated in CF vs. non-CF cells and that it negatively regulates wt-CFTR expression and function. Of note, F508del-CFTR expressing cells are insensitive to KLF4 modulation. Next, we investigated which KLF4-related pathways have an effect on CFTR. Our data also show that KLF4 modulates wt-CFTR (but not F508del-CFTR) via both the serine/threonine kinase AKT1 (AKT) and glycogen synthase kinase 3 beta (GSK3 beta) signaling. While AKT acts positively, GSK3 beta is a negative regulator of CFTR. This crosstalk between wt-CFTR and KLF4 via AKT/ GSK3 beta signaling, which is disrupted in CF, constitutes a novel mechanism linking CFTR to the epithelial differentiation.