Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma / 医学前沿

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

Morphometry of the Hand Knob Region and Motor Function Change in Eloquent Area Glioma Patients.

PURPOSE: The hand knob area is the cortical representation of motor hand function. The current study aimed to investigate the effects of eloquent area gliomas on the morphometry of the hand motor cortex and preoperative hand motor function. METHODS: A retrospective study of 320 glioma patients was conducted. Seventy-eight patients with gliomas involving motor functional area were finally enrolled. Using axial T2-weight magnetic resonance images, the width and height of the hand knob were measured in both hemispheres, and differences were compared between the affected and unaffected hemispheres. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to estimate the degree of correlation between distance measurements and motor impairment. RESULTS: The width and height of the hand knob in the affected and unaffected hemispheres were significantly different (p < 0.0001). The width, height and distance from the tumor to hand knob were reduced in the functionally impaired group compared to the unimpaired group (p = 0.0003, p < 0.0001, p = 0.0005, respectively). The three parameters were significantly correlated and remained significant in ROC and logistic regression analysis. The optimal cut-off value of width, height and distance for identifying preoperative hand muscle strength were 5.73 mm, 5.80 mm and 5.92 mm, respectively. CONCLUSION: The morphometry of the hand knob is often changed by the infiltration or extrusion of the tumors that were located in or near the hand knob. The width, height of hand knob and the distance from tumor to hand knob could serve as anatomic biomarkers related to preoperative neurological motor deficits.