scholarly journals P04.13 Prognostic role of single stranded DNA binding protein 2 in IDH wild type lower grade glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii31-iii31
Author(s):  
Y Chai ◽  
W Liu ◽  
L Hu ◽  
Y Zhang ◽  
P Liang

Abstract Comprehensive and integrative characterizations of genomic analysis including somatic alterations and molecular subtypes of glioma have been established. However, diffuse gliomas (World Health Organization grades II and III, hereafter referred to collectively as lower-grade gliomas,LGG) consist of highly variable clinical behaviors, leading to emerging studies to identify prognostic factors. Through comparative analyses of 516 cases of primary LGG patients from The Cancer Genome Atlas (TCGA) dataset, we reported that the expression level and methylation level of SSBP2 (encoding single stranded DNA-binding protein 2) gene vary among LGG patients and SSBP2 expression or gene body methylation can be served as prognostic biomarkers for LGG survival. Cox regression results confirmed that SSBP2 as an independent predictor of survival in LGG, with a cox coefficient of 0.534 indicating a worse prognosis. Furthermore, lower-grade glioma was statistically ranked first among 21 different cancer types according to the FDR correction. We further investigated the combination of SSBP2 with other known genetic prognostic factors(IDH mutation and 1p19q co-deletion) of LGG. By matching gene expression profile of LGG patients, IDH-mutant gliomas had decreased expression of SSBP2 compared with IDH-wildtype gliomas and 1p19q intact gliomas had increased expression of SSBP2 compared with 1p19q codeletion gliomas. Moreover, we found that the combination of IDH or 1p19q status with SSBP2 identified LGG subsets with significantly diverse survival effects. Patients with low SSBP2 expression had significantly better 5-, 10-, and 15-year OS in IDH wild type, but not in the cohorts of IDH mutant. Our findings offer an explanation for the specificity of SSBP2 effect on survival rate in IDH wild type LGG patients.

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1503-1512 ◽  
Author(s):  
Roy A Khalaf ◽  
Richard S Zitomer

AbstractWe have identified a repressor of hyphal growth in the pathogenic yeast Candida albicans. The gene was originally cloned in an attempt to characterize the homologue of the Saccharomyces cerevisiae Rox1, a repressor of hypoxic genes. Rox1 is an HMG-domain, DNA binding protein with a repression domain that recruits the Tup1/Ssn6 general repression complex to achieve repression. The C. albicans clone also encoded an HMG protein that was capable of repression of a hypoxic gene in a S. cerevisiae rox1 deletion strain. Gel retardation experiments using the purified HMG domain of this protein demonstrated that it was capable of binding specifically to a S. cerevisiae hypoxic operator DNA sequence. These data seemed to indicate that this gene encoded a hypoxic repressor. However, surprisingly, when a homozygous deletion was generated in C. albicans, the cells became constitutive for hyphal growth. This phenotype was rescued by the reintroduction of the wild-type gene on a plasmid, proving that the hyphal growth phenotype was due to the deletion and not a secondary mutation. Furthermore, oxygen repression of the hypoxic HEM13 gene was not affected by the deletion nor was this putative ROX1 gene regulated positively by oxygen as is the case for the S. cerevisiae gene. All these data indicate that this gene, now designated RFG1 for Repressor of Filamentous Growth, is a repressor of genes required for hyphal growth and not a hypoxic repressor.


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