HighlightsR. pusillus encodes cellulose-, xylan- and chitin-degrading proteins.Two putative GH9 endoglucanases were identified.Enzyme system of R. pusillus is suited to consume easily accessible sugars.Endoglucanase and xylanase activity detected when the fungus was grown on wheat bran and xylan.
Purpose The presence of epithelial cells is a bad prognostic factor in uveal melanoma (UM) and epithelial tumors are characterized by high expression of E‐cadherin. However, CDH1, the gene encoding for E‐cadherin, is located at chromosome 16q which is lost in UM with a bad prognosis. In order to solve this paradox we studied the underlying epigenetic mechanism of the spindle to epithelial transition and the accompanying E‐cadherin expression. Methods UM cell lines were in vitro treated with methylation and deacetylation inhibitors, or were cultured under hypoxic conditions to mimic in vivo UM conditions to induce epigenetic reprogramming. RNA and DNA was isolated for gene expression, DNA methylation, and chromosome structure analysis, while cell lysates were used for E‐cadherin analysis. Results Treatment with methylation and deacetylation inhibitors resulted in a phenotypic change from a spindle to more epithelial cell type. Furthermore, inhibition of methylation and hypoxia treatment both upregulated E‐cadherin expression in vitro and induced euchromatin formation at 16q22, where CDH1 is located. Conclusion By revealing epigenetic regulation of CDH1 in UM we resolve a step in the dynamic process of spindle to epitheloid celltype switch in UM. Since this switch could be induced by hypoxia we establish a link between environmental stress and progression. With these data we provide evidence for epigenetic regulation of UM progression as well as an option for future treatment.
We report here the annotated draft genome sequence of the thermophilic biomass-degrading fungus Malbranchea cinnamomea strain FCH 10.5, isolated from compost at a waste treatment plant in Vietnam. The genome sequence contains 24.96 Mb with an overall GC content of 49.79% and comprises 9,437 protein-coding genes.
Purpose Chromosomal aberrations and the inflammatory phenotype have been identified as predictive factors for survival of uveal melanoma (UM). The mechanism by which these factors are linked remains obscure. We took the human leukocyte antigen (HLA), located on chromosome 6p as marker for inflammation and studied whether aberrations of chromosome 6p influenced the HLA expression in UM. Methods SNP‐array copy number analysis and gene expression profiling were performed on 28 uveal melanomas of patients who underwent enucleation between 1999 and 2004 at the Leiden University Medical Center, Leiden, in The Netherlands. UM protein expression of HLA‐A, ‐B and –DR was measured with immunohistochemistry. The status of chromosome 3, 6p, and gene expression of HLA and HLA regulators were analyzed, as well as protein expression of HLA. Results Gain of 6p was present in 8 cases (29%) and not related with survival. An increased gene expression was seen in the group who died due to metastatic UM for HLA‐A and –B, and B2M. Gene expression correlated with protein expression for HLA‐A, HLA‐B, but not with HLA‐DR. Tumors did not differ in level of HLA protein expression, HLA gene expression, and HLA regulator gene expression with regard to chromosome 6p status. Conclusion High HLA gene‐ and protein expression in UM are not influenced by gain of 6p. Yet for the first time we demonstrated that in UM an increased expression of HLA class I genes correlated with the elevated protein expression of HLA class I.
Background: Uveal melanoma (UM) development and progression is correlated with specific molecular changes. Recurrent mutations in GNAQ and GNA11 initiate UM development while tumour progression is correlated with monosomy of chromosome 3 and gain of chromosome 8q. Hence, molecular analysis of UM is useful for diagnosis and prognosis. The aim of this study is to evaluate the use of digital PCR (dPCR) for molecular analysis of UM. Methods: A series of 66 UM was analysed with dPCR for three hotspot mutations in GNAQ/GNA11 with mutation specific probes. The status of chromosomes 3 and 8 were analysed with genomic probes. The results of dPCR analysis were cross-validated with Sanger sequencing, SNP array analysis, and karyotyping. Results: Using dPCR, we were able to determine the molecular profile of 66 enucleated UM. With digital PCR, GNAQ/GNA11 mutations were detected in 60 of the 66 UM. Sanger sequencing revealed three rare variants, and, combined, these assays revealed GNAQ/GNA11 mutations in 95% of UM. Monosomy 3 was present in 43 and chromosome 8 aberrations in 52 of the 66 UM, with dPCR and SNP results showing an excellent correlation (for monosomy 3 r = 0.921, for 8q gain r = 0.922). Survival analysis showed that increasing 8q copy numbers were positively correlated with metastasis risk. Conclusion: Molecular analysis with dPCR is fast and sensitive. Just like the recurrent genomic aberrations of chromosome 3 and 8, hotspot mutations in GNAQ and GNA11 are effectively detected in heterogeneous samples. Increased sensitivity contributes to the number of mutations and chromosomal aberrations detected. Moreover, quantification of copy number with dPCR validated 8q dosage as a sensitive prognostic tool in UM, of which implementation in disease prediction models will further improve prognostication. Citation Format: Mark J. de Lange, Mieke Versluis, Sake van Pelt, Claudia A.L. Ruivenkamp, Wilma G. Kroes, Jinfeng Cao, Martine J. Jager, Gre P.M. Luyten, Pieter A. van der Velden. Digital PCR validates 8q dosage as prognostic tool in uveal melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 595. doi:10.1158/1538-7445.AM2015-595
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