A novel SETD3-ALK fusion in lung adenocarcinoma and sustained clinical response to crizotinib.

OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a vital driving mutation in non-small cell lung cancer (NSCLC). ALK rearrangements may involve different breakpoints and multiple fusion partners, presenting different therapeutic responses. There are no standard treatment options for rare ALK rearrangements. Here, we report a case of advanced lung adenocarcinoma (LUAD) harboring a novel SET domain containing 3 (SETD3)-ALK fusion and sensitive to crizotinib, which has not been previously reported. MATERIALS AND METHODS: Molecular and pathological features were confirmed using percutaneous lung biopsy guided by computed tomography (CT), immunohistochemical (IHC) staining and next-generation sequencing (NGS). RESULTS: NGS revealed that a novel SETD3-ALK fusion was detected in the patient with LUAD, and IHC analysis confirmed that this fusion had functional expression. The patient had a progression-free survival (PFS) over 16 months after crizotinib treatment (250 mg b.i.d.), with ongoing clinical response. CONCLUSION: This case introduces a novel and meaningful ALK fusion type in LUAD with sustained sensitivity to crizotinib, providing a reference to the treatment of similar cases with SETD3-ALK fusion in the future.

Suppression of Fusarium oxysporum and induced resistance of plants involved in the biocontrol of Cucumber Fusarium Wilt by Streptomyces bikiniensis HD-087.

Cucumber Fusarium Wilt, caused by Fusarium oxysporum f. sp. cucumerinum, which usually leads to severe economic damage, is a common destructive disease worldwide. To date, no effective method has yet been found to counteract this disease. A fungal isolate, designated HD-087, which was identified as Streptomyces bikiniensis using physiological-biochemical identification and 16S rRNA sequence analysis, is shown to possess distinctive inhibitory activity against F. oxysporum. The fermentation broth of HD-087 leads to certain abnormalities in pathogen hyphae. It peroxidizes cell membrane lipids, which leads to membrane destruction along with cytoplasm leakage. This broth also restrains germination of the conidia. The activities of the enzymes peroxidase, phenylalanine ammonia-lyase, and ß-1,3-glucanase in cucumber leaves were dramatically increased after treated with fermentation broth of HD-087. The levels of chlorophyll and soluble sugars were also found to be increased, with the relative conductivity of leaves being reduced. In short, the metabolites of strain HD-087 can effectively suppress F. oxysporum and trigger induced resistance in cucumber.

Development of a highly efficient gene targeting system allowing rapid genetic manipulations in Penicillium decumbens.

Penicillium decumbens is an important industrial filamentous fungus and has been widely used in biorefinery due to its high production of cellulase and hemicellulase. However, molecular engineering has still rarely been applied for strain improvement in P. decumbens. It has been proven that gene targeting manipulation in many filamentous fungi is hampered by nonhomologous end-joining (NHEJ) pathway. To improve gene targeting efficiency in P. decumbens, the putative pku70 encoding the Ku70 homologue involved in the NHEJ pathway was identified and deleted. The Deltapku70 strain showed no apparent defect in vegetative growth, conidiation, and cellulase production, and displayed similar sensitivity to chemical agents of hygromycin B, ethyl methane sulfonate, and H2O2 at different concentrations compared with the wild-type strain. The effect of the absence of pku70 on gene targeting was tested by disruption of creA encoding a putative carbon catabolite repressor and xlnR encoding a putative transcriptional activator. Efficiency of gene targeting for both genes was 100% in the Deltapku70 strain, compared with the low efficiency in the wild-type recipient. Furthermore, the integration types for three single targeting cassettes and the cotransformation of two independent targeting cassettes were primarily investigated in P. decumbens. The highly efficient gene targeting system established in this study will open the way to large-scale functional genomic analysis in P. decumbens and contribute to the study of the mechanism of lignocellulose degradation by P. decumbens.