Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

Cell Cycle-Related FAM64A Could be Activated by TGF-ß Signaling to Promote Glioma Progression.

Gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. FAM64A, a cell cycle-related gene, has been found to promote cell proliferation in various tumors, including gliomas. However, the regulatory mechanism and clinical significance of FAM64A in gliomas remain unclear. In this study, we investigated FAM64A expression in gliomas with different grades and constructed FAM64A silenced cell lines to study its functions. Our results demonstrated that FAM64A was highly expressed in glioblastoma (P < 0.001) and associated with a poor prognosis (P < 0.001). Expression profiles at the single-cell resolution indicated FAM64A could play a role in a cell-cycle-dependent way to promote glioma cell proliferation. We further observed that FAM64A silencing in glioma cells resulted in disrupted proliferation and migration ability, and increased cell accumulation in the G2/M phase (P = 0.034). Additionally, TGF-ß signaling upregulates FAM64A expression, and SMAD4 and FAM64A co-localize in high-grade glioma tissues. We found FAM64A knockdown inhibited TGF-ß-induced epithelial-mesenchymal transition in glioma. Our findings suggest that FAM64A could serve as a diagnostic and therapeutic target in gliomas.

Discovery and Verification of an Immune-Related Gene Pairs Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma.

The study of IRGPs to construct the prognostic signature in head and neck squamous cell carcinoma (HNSCC) has not yet elucidated. The objective of this study was to explore a novel model to predict the prognosis of HNSCC patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were set as training and validation cohorts, respectively. The least absolute shrinkage and selection operator (LASSO) and time-dependent ROC were employed to screen the highest frequency immune-related gene pairs (IRGPs) and their best cut-off value. Survival analysis, Cox regression analysis were applied to discover the effects of selected IRGPs signature on survival outcomes. The immune cell proportions were deconvoluted by the CIBERSORT method. After a couple of filtering, we obtained 22 highest frequency IRGPs. The overall survival time of HNSCC patients with a high score of IRGPs was shorter as compared to the ones with a low score in two independent datasets (P < 0.001). Six kinds of immune cells were found to be differentially distributed in the two different risk groups of HNSCC patients (P < 0.001). GO and GSEA analysis showed these differentially expressed genes enriched in multiple molecular functions. The new IRGPs signature probably confers a new insight into the prognosis prediction of HNSCC patients.

Genomic analysis of primary and recurrent gliomas reveals clinical outcome related molecular features.

Tremendous efforts have been made to explore biomarkers for classification and grading on gliomas. The goal of this study was to identify more molecular features that are associated with clinical outcomes by comparing the genomic profiles of primary and recurrent gliomas and determine potential recurrence leading factors that are significantly enriched in relapse tumors. Hybrid capture based next generation sequencing (NGS) analysis was performed on 64 primary and 17 recurrent glioma biopsies. Copy number variation (CNV) was more frequent in recurrent tumors and CDKN2A/B loss was significantly enriched. In addition, overall mutations in cell cycle pathway are more common in relapse tumors. The patterns of gene sets, including IDH1/TERT and IDH1/TP53 exhibited significant difference between the groups. Survival analysis uncovered the worse disease-free survival (DFS) and overall survival (OS) associated with altered copy number and excessive activation of CELL CYCLE pathway. High Tumor Mutation Burden (TMB) was also a biomarker with great potential for poor prognosis. The assessment of genomic characteristics in primary versus recurrent gliomas aids the discovery of potential predictive biomarkers. The prognostic value of TMB in gliomas was raised for the first time.

[Chondrosarcoma original from the zygomatic arch: A case report and literature review].

Chondrosarcoma original from the zygomatic arch is a very rare disease with high malignancy. Surgery is the main means of treatment at present for duo to its poor sensitivity to radiochemotherapy. We reported a young patient who was recovery well in a 4-years follow-up without radiochemotherapy after a total resection of the tumor.