scholarly journals Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas

Oncogene ◽  
1998 ◽  
Vol 16 (25) ◽  
pp. 3331-3335 ◽  
Author(s):  
Daniel Maier ◽  
Zuwen Zhang ◽  
Elisabeth Taylor ◽  
Marie-France Hamou ◽  
Otmar Gratzl ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Karrie Mei-Yee Kiang ◽  
Stella Sun ◽  
Gilberto Ka-Kit Leung

Loss of heterozygosity (LOH) on chromosome 10 frequently occurs in gliomas. Whereas genetic loci with allelic deletion often implicate tumor suppressor genes, a putative tumor suppressor Adducin3 (ADD3) mapped to chromosome 10q25.2 was found to be preferentially downregulated in high-grade gliomas compared with low-grade lesions. In this study, we unveil how the assessment of ADD3 deletion provides clinical significance in glioblastoma (GBM). By deletion mapping, we assessed the frequency of LOH in forty-three glioma specimens using five microsatellite markers spanning chromosome 10q23-10qter. Data were validated in The Cancer Genome Atlas (TCGA) cohort with 203 GBM patients. We found that allelic loss in both D10S173 (ADD3/MXI1 locus) and D10S1137 (MGMT locus) were positively associated with tumor grading and proliferative index (MIB-1). However, LOH events at only the ADD3/MXI1 locus provided prognostic significance with a marked reduction in patient survival and appeared to have diagnostic potential in differentiating high-grade gliomas from low-grade ones. Furthermore, we showed progressive loss of ADD3 in six out of seven patient-paired gliomas with malignant progression, as well as in recurrent GBMs. These findings suggest the significance of ADD3/MXI1 locus as a promising marker that can be used to refine the LOH10q assessment. Data further suggest the role of ADD3 as a novel tumor suppressor, whereby the loss of ADD3 is indicative of a progressive disease that may at least partially account for rapid disease progression in GBM. This study revealed for the first time the downregulation of ADD3 on the genetic level resulting from copy number deletion.


2021 ◽  
pp. 1-8
Author(s):  
Haimei Cao ◽  
Xiang Xiao ◽  
Jun Hua ◽  
Guanglong Huang ◽  
Wenle He ◽  
...  

Objectives: The present study aimed to study whether combined inflow-based vascular-space-occupancy (iVASO) MR imaging (MRI) and diffusion-weighted imaging (DWI) improve the diagnostic accuracy in the preoperative grading of gliomas. Methods: Fifty-one patients with histopathologically confirmed diffuse gliomas underwent preoperative structural MRI, iVASO, and DWI. We performed 2 qualitative consensus reviews: (1) structural MR images alone and (2) structural MR images with iVASO and DWI. Relative arteriolar cerebral blood volume (rCBVa) and minimum apparent diffusion coefficient (mADC) were compared between low-grade and high-grade gliomas. Receiver operating characteristic (ROC) curve analysis was performed to compare the tumor grading efficiency of rCBVa, mADC, and the combination of the two parameters. Results: Two observers diagnosed accurate tumor grade in 40 of 51 (78.4%) patients in the first review and in 46 of 51 (90.2%) in the second review. Both rCBVa and mADC showed significant differences between low-grade and high-grade gliomas. ROC analysis gave a threshold value of 1.52 for rCBVa and 0.85 × 10−3 mm2/s for mADC to provide a sensitivity and specificity of 88.0 and 81.2% and 100.0 and 68.7%, respectively. The area under the ROC curve (AUC) was 0.87 and 0.85 for rCBVa and mADC, respectively. The combination of rCBVa and mADC values increased the AUC to 0.92. Conclusion: The combined application of iVASO and DWI may improve the diagnostic accuracy of glioma grading.


2020 ◽  
Vol 79 (10) ◽  
pp. 1038-1043
Author(s):  
Meaghan Morris ◽  
Meghan Driscoll ◽  
John W Henson ◽  
Charles Cobbs ◽  
LiQun Jiang ◽  
...  

Abstract Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.


2016 ◽  
Vol 29 (5) ◽  
pp. 400-407 ◽  
Author(s):  
Lamiaa El-Serougy ◽  
Ahmed Abdel Khalek Abdel Razek ◽  
Amani Ezzat ◽  
Hany Eldawoody ◽  
Ahmad El-Morsy

1999 ◽  
Vol 81 (8) ◽  
pp. 1371-1377 ◽  
Author(s):  
S Balesaria ◽  
C Brock ◽  
M Bower ◽  
J Clark ◽  
S K Nicholson ◽  
...  

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Li-qiang Liu ◽  
Li-fei Feng ◽  
Cheng-rui Nan ◽  
Zong-mao Zhao

The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR. Survival rates for population of the CREB3L1- and PTN-presenting patients were examined. CREB3L1+ cell counts were decreased with increased PTN+ cells in the low-grade and high-grade glioma tissues as compared with the control. Population proportion of the CREB3L1+-presenting patients decreased from the control to the high-grade glioma and the population of the PTN+-presenting patients increased in low- and high-grade gliomas as compared with the control (both P<0.05). The decrease in the CREB3L1 mRNA expression was associated with the increase in the PTN mRNA expression in the low- and high-grade gliomas (P<0.05). Survival time for patients with CREB3L1− and PTN+ gliomas was shorter than patients with CREB3L1+ and PTN− gliomas in the investigated cohorts (both P<0.05). There was a relationship between the expression levels of both proteins and survival time. CREB3L1 and PTN expression levels serve as biomarkers with utility in grading gliomas. Absence of CREB3L1 and presence of PTN in brain glioma cells correlate with survival time of the glioma patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yuankai Lin ◽  
Jianrui Li ◽  
Zhiqiang Zhang ◽  
Qiang Xu ◽  
Zhenyu Zhou ◽  
...  

Gliomas grading is important for treatment plan; we aimed to investigate the application of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in gliomas grading, by comparing with the three-dimensional pseudocontinuous arterial spin labeling (3D pCASL). 24 patients (13 high grade gliomas and 11 low grade gliomas) underwent IVIM DWI and 3D pCASL imaging before operation; maps of fast diffusion coefficient (D∗), slow diffusion coefficient (D), fractional perfusion-related volume (f), and apparent diffusion coefficient (ADC) as well as cerebral blood flow (CBF) were calculated and then coregistered to generate the corresponding parameter values. We found CBF andD∗were higher in the high grade gliomas, whereas ADC,D, andfwere lower (allP<0.05). In differentiating the high from low grade gliomas, the maximum areas under the curves (AUC) ofD∗, CBF, and ADC were 0.857, 0.85, and 0.902, respectively. CBF was negatively correlated withfin tumor (r=-0.619,P=0.001). ADC was positively correlated withDin both tumor and white matter (r=0.887,P=0.000andr=0.824,P=0.000, resp.). There was no correlation between CBF andD∗in both tumor and white matter (P>0.05). IVIM DWI showed more efficiency than 3D pCASL but less validity than conventional DWI in differentiating the high from low grade gliomas.


2020 ◽  
Author(s):  
Raksha A. Ganesh ◽  
Jayashree V. Raghavan ◽  
Pranali Sonpatki ◽  
Divya Naik ◽  
Priyanka Arunachalam ◽  
...  

AbstractGliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.


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