Search

Glioblastoma (GBM) is the most malignant primary brain tumor in adults with substantial genomic alterations. The median survival is approximately 14.6 months, despite aggressive therapeutic intervention, which comprised of surgical resection, radiotherapy, and chemotherapy. Recent studies on cancer genomic have revealed crucial insights into dynamic molecular subgroups within GBM, which govern distinct clinical response and sensitivity of each individual to therapy. In the present study, we analyzed genomic composition of primary GBMs between two ethnic groups [IRCR (Institute of Refractory Cancer Research), and TCGA (The Cancer Genome Atlats)] to explore genomic and molecular features that constitute malignant behavior of glioblastoma based on distinct ethnicity. We identified enrichments of MAPK and p53 pathways in IRCR patients, while aberrant activation of Receptor Tyrosine Kinases (RTKs) were predominant in TCGA cohort. We also discovered differential clinical prognosis between two groups and explored essential features that present such diversity., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Genome-wide association studies have identified the susceptibility single nucleotide polymorphisms (SNPs) of glioma at chromosome 20q13.33, and the replication study conducted among Chinese Han population also confirmed the susceptibility locus rs6010620 is located in this region. To identify other genetic variants in 20q13.33, we genotyped 13 common tagging SNPs and imputed 86 additional SNPs in a region ∼100 kb at 20q13.33 among 1027 controls and 987 cases. Among 99 SNPs, five independent susceptibility loci (20-62315594 in RTEL1, 20-62335293 in adenosine diphosphate ribosylation factor-related protein 1, rs3761121 in ZGPAT, rs1058319 in SLC2A4RG and rs5019252 in ZBTB46) were identified for glioma. Two of the five SNPs (20-62335293, P = 3.09 × 10(-10) and rs1058319, P = 1.26 × 10(-11)) satisfied the threshold of genome-wide significance (P < 10(-8)). Further stratified analysis revealed that 20-62315594 was only significantly associated with glioblastoma (GBM) risk [P = 1.71 × 10(-8) for trend test, adjusted odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.57-2.52]. Other four SNPs were significantly associated with both GBM and astrocytoma. The risk of glioma increased with the increase of the number of risk alleles (P = 1.94 × 10(-11), for trend test, adjusted OR = 1.43, 95% CI = 1.29-1.58), and the individuals who carried 7-10 risk alleles had a 2.64-fold increased risk of glioma development compared with those who carried 0 risk allele (P = 8.71 × 10(-7), adjusted OR = 2.64, 95% CI = 1.79-3.88). Our results indicated a complex effect contributing to glioma risk at 20q13.33, which may provide a new insight into glioma development. Both variants and genes in this region should be considered in future studies designed to investigate the biological functions.

Background: The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression. Recently, the APE1/Ref-1 promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of APE1/Ref-1 in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes., Methods: The APE1/Ref-1 -141T/G polymorphism was analyzed in a case-control study including 766 glioma patients (among them 241 glioblastoma, 284 astrocytomas except for glioblastoma and 241 other gliomas) and 824 cancer-free controls from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele-specific MALDI-TOF mass spectrometry assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. A test of trend was calculated using the genotype as an ordinal variable in the regression model. For each statistically significant association identified, we estimated the false positive reporting probability (FPRP). FPRP values less than 0.2 were consider to indicate robust associations., Results: The significant association between the APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk (OR = 0.80, 95% CI = 0.65-0.98, P = 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, P = 0.012), compared with the TT homozygote. This result remained robust given the prior probabilities of 25% (FPRP = 0.052) and 10% (FPRP = 0.140), but not with a prior probability of 1% (FPRP = 0.643). The P-associated with the trend test was 0.014., Conclusions: Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.

Astrocytic tumors are the most frequent primary brain neoplasms. They are clinically characterized by wide variations in histology. Analysis of chromosome DNA imbalance may help to advance diagnosis, grading, and classification, and to determine appropriate therapeutic approaches for tumors of astrocytic lineages. Comparative genomic hybridization (CGH) provides comprehensive information about chromosome DNA aberrations, and is an important technique for evaluating the differences at genomic levels among the same or different grade tumors. In this study, 63 astrocytic tumors of Chinese patients were screened by CGH, and the relationship between their chromosome DNA imbalances and the histopathological classification, grading, and clinical features was analyzed. Most tumors showed genomic copy aberrations detected by CGH. The most frequent abnormalities were regional gains in chromosome 1q and 7p; regional losses in chromosome 1p, 2q, 4q, 6p, 10q, 12q, 15q, 19q, and 22q were also frequently observed. The gain of 1q and the loss of 15q were relevant to the histological types and grades of WHO classification. The losses of 4q and 10q correlated with age in the group of anaplastic astrocytoma, which was unreported in the literature. This study confirmed that chromosomal aberrations, such as +1q, -4q, -10q, +7p, and -15q possibly contributed to the pathogenesis of these tumors. Our data was the first report on the chromosomal aberrations of astrocytic tumors of Chinese patients., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Background: Epidermal growth factor (EGF) is critical in cancer process. EGF and EGF receptor (EGFR) interaction plays a pivotal role in cell proliferation, differentiation, and tumorigenesis of epithelial tissues. Variations of the EGF +61G/A (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to brain glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population., Methods: In this study, we analyzed single nucleotide polymorphism of EGF +61G/A in 677 patients with glioma and 698 gender- and age-matched controls. Genotyping was performed by polymerase chain reaction-ligation detection reaction (PCR-LDR) method., Results: The A allele (minor Allele) was 33.0% in cases and 27.3% in controls. The additive model was more powerful to reveal the association in our study than that of recessive and dominant model. Our data showed the genotype G/A and A/A was associated with increased risk for glioma (adjusted OR = 1.48, 95%CI: 1.17-1.87, p = 0.001 for G/A, adjusted OR = 1.81, 95%CI: 1.20-2.72, p = 0.005 for A/A, respectively), and for glioblastoma (adjusted OR = 1.51, 95%CI: 1.06-2.17, p = 0.024 and adjusted OR = 2.35, 95%CI: 1.34-4.15, p = 0.003, respectively). The A allele significantly increased glioma risk (OR = 1.31, 95%CI: 1.11-1.55, p = 0.001). The additive model (G/G vs G/A vs A/A) showed that both G/A and A/A genotype increased glioma risk (adjusted OR = 1.40, 95% CI: 1.17-1.66, p = 0.0002).G/A and A/A genotypes or EGF +61 A allele increased risk in both low and high WHO grade glioma. Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers., Conclusions: Our study indicated that G/A and A/A genotypes or EGF +61 A allele were associated with higher glioma risk in Chinese. This is in contrast with previous studies which reported G allele as a risk factor of glioma in Caucasian. The role of EGF +61 A/G polymorphism in glioma susceptibility needs further investigation.

The authors propose "decreased-dose-intensity" PCV (procarbazine, lomustine [CCNU], and vincristine) chemotherapy for Asian patients with oligodendroglial tumors. In this study, all seven patients with oligodendroglioma (OD) and eight with anaplastic oligodendroglioma (AO) had objective responses or stable disease. Median progression-free survival was greater than 29 months (OD) and 36.5 months or greater (AO); 86% of patients with OD and 63% with AO remain progression-free. Twenty-four Common Toxicity Criteria Grade 3/4 adverse events were noted.

We report a rare case of glioblastoma that was definitely congenital. Most congenital glioblastomas arise in the cerebral hemispheres. Four cases of congenital glioblastoma have been reported in the literature from Asian countries, two from Japan and the others from Korea. Two Japanese cases arose in the cerebello-pontine angle, and a cerebellar hemisphere, respectively. In contrast, both known Korean cases and Euro-American cases arose in cerebral hemispheres. Surprisingly, the parents of the present patient were Korean. When we reviewed the world literature on congenital glioblastomas, we recognized that in Japanese patients this tumor did not tend to occur in a cerebral hemisphere. This deviation of the localization may have biological reasons, such as genetic or environmental factors.