Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Diagnostic value of cancer-testis antigen mRNA in peripheral blood from hepatocellular carcinoma patients

AIM: To evaluate the diagnostic value of cancer-testis antigen (CTA) mRNA in peripheral blood samples from hepatocellular carcinoma (HCC) patients

Choroid plexus tumours on MRI: similarities and distinctions in different grades

Abstract Background The therapeutic planning varies for different grades of choroid plexus tumours (CPTs). The aim of this study was to define the similarities and distinctions among MRIs for different grades of CPTs, providing more guidance for clinical decisions. Methods We reviewed the MRI findings in 35 patients with CPT verified by surgical pathology, including 18 choroid plexus papillomas (CPPs, grade I), 11 atypical choroid plexus papillomas (aCPPs, grade II), and 6 choroid plexus carcinomas (CPCs, grade III). Nonparametric testing based on ranks was performed to evaluate the association of pathological grade with MRI findings. Results Among the 35 CPTs, 29 were located in the ventricular system. The tumours were generally slightly hypo- or isointense on T1WI, slightly hyper- or isointense on T2WI, and moderately or strongly enhanced in post-contrast imaging. Twenty cases were accompanied by hydrocephalus. The median tumour longest diameters of CPPs, aCPPs, and CPCs were 28.6, 44.6, and 60.6 mm, respectively. Four cases were purely cystic, 6 were papillary, 10 were lobulated, and 2 were irregular. Three cases had necrosis. The median oedema diameters of CPPs, aCPPs, and CPCs were 0, 0, and 24.1 mm, respectively. The grades of CPTs were statistically associated with tumour longest diameter (r s  = 0.68, P < 0.001), internal morphology (χ 2 = 10.32, P = 0.016), necrosis (Z = 2.27, P = 0.023), and oedema diameter (r s  = 0.72, P < 0.001). Conclusion CPTs typically appeared as intraventricular papillary or lobulated lesions, often accompanied by hydrocephalus. Larger tumour, irregular or fuzzy internal morphology, presentation of necrosis and wide-ranging peritumoural oedema might increase the likelihood of malignancy

G-protein Coupled Receptor 34 Knockdown Impairs the Proliferation and Migration of HGC-27 Gastric Cancer Cells In Vitro

Background: Overexpression of G-protein coupled receptor 34 (GPR34) affects the progression and prognosis of human gastric adenocarcinoma, however, the role of GPR34 in gastric cancer development and progression has not been well-determined. The current study aimed to investigate the effect of GPR34 knockdown on the proliferation, migration, and apoptosis of HGC-27 gastric cancer cells and the underlying mechanisms. Methods: The expression of GPR34 in gastric cancer cell line HGC-27 was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. HGC-27 cells were employed to construct the stable GPR34 knockdown cell model in this study. Real-time RT-PCR and Western blotting were applied to validate the effect of short hairpin RNA (ShRNA) on the expression of GPR34 in HGC-27 gastric cells. The proliferation, migration of these cells were examined by Cell Counting Kit-8 and transwell. We also measured expression profile of PI3K/PDK1/AKT and ERK using Western blotting. Results: The ShRNA directed against GPR34 effectively inhibited both endogenous mRNA and protein expression levels of GPR34, and significantly down-regulated the expression of PIK3CB (P < 0.01), PIK3CD (P < 0.01), PDK1 (P < 0.01), phosphorylation of PDK1 (P < 0.01), Akt (P < 0.01), and ERK (P < 0.01). Furthermore, GPR34 knockdown resulted in an obvious reduction in HGC-27 cancer cell proliferation and migration activity (P < 0.01). Conclusions: GPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer

Inactivation Kinetics of beta-N-Acetyl-D-glucosaminidase from Green Crab (Scylla serrata) by Guanidinium Chloride

National Foundation for fostering talents of basic science [J1030626]; China Natural Science Foundation of Nation [40576066]; Program for Innovative Research Team in Science and Technology in Fujian Province Universitybeta-N-acetyl-D-glucosaminidase (NAGase) is a major member in chitinolytic enzymes system, which plays an important role in the hatching and molting processes of marine organism. The effects of guanidinium chloride (GuHCl) on the activity of NAGase from green crab (Scylla serrata) were investigated in this study. In results, GuHCl causes reversible inactivation of the enzyme at below 0.8 M concentrations, and the IC50 is estimated to be 0.15 M. The relationship between the enzyme activity and conformation was charaterized by monitoring the change of protein fluorescence spectra. With increasing GuHCl concentration, the fluorescence intensity of the enzyme distinctly decreases, and the maximal emission peaks appear red-shifted (from 338 nm to 343 nm). The enzyme inactivation precedes conformational changes, indicating that the enzyme active site is more flexible than the whole enzyme molecule. The result of the kinetics of inactivation shows that the value of k(+0) is larger than that of k'(+0). It suggests that the substrate could protect the enzyme to a certain extent during guanidine denaturation. Our results provide important new insights in marine organism culture, especially in crustacean growth