Prognostic relevance of genetic alterations in diffuse lower-grade gliomas

Abstract

Subtype-specific genetic lesions can be used to stratify patients within each LGG subtype. enabling better prognostication and management.

Prognostic significance of genetic biomarkers in isocitrate dehydrogenase‐wild‐type lower‐grade glioma: the need to further stratify this tumor entity – a meta‐analysis

“…gain of chromosome 7 and loss of chromosome 10) has been reported in gliomas . Gain of chromosome 7 and loss of chromosome 10 were shown to be independent prognostic factors in IDH ‐wt LGGs adjusted for age and WHO grade . Nearly all IDH ‐wt LGGs with chromosome 7 gain and chromosome 10 loss harbored TERT promoter mutation , which was a prognostic indicator in this tumor entity based on our results.…”

“…After screening the abstract, 150 potential articles were selected for full-text reading and, finally, we included 11 studies comprising 911 IDH-wt LGGs for final analyses (Fig. 1) [5,[7][8][9][10][11][12][13][14][15][16]. The characteristics of these studies are described in Tables 1 and 2.…”

cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”

“…These conclusions are based on the findings that those histologic IDH-wildtype diffuse astrocytic gliomas of WHO grade II or III that carry EGFR amplification, +7/−10 or TERT promoter mutation are associated with significantly shorter patient survival compared to patients with other WHO grade II or III gliomas, and patients have outcomes similar to patients with IDH-wildtype glioblastoma [1, 2, 11, 26, 27, 32, 33]. The large majority of IDH-wildtype diffuse astrocytic gliomas of WHO grade II or III with these genetic signatures correspond histologically to anaplastic astrocytoma, WHO grade III.…”

“…BRAF V600E) may be warranted in diagnostically challenging cases [27]. Some studies have reported on gains of 7p or 7q, as well as losses of 10p or 10q as chromosomal imbalances linked to poor survival for patients with WHO grade II or III IDH-wildtype astrocytic gliomas [2, 27, 29, 32, 33]. However, most studies reported whole gains of chromosome 7 and whole losses of chromosome 10 (+7/−10), and the prognostic association of other, far less common imbalances, such as +7q/−10q, +7/−10q or +7q/−10, was not evaluated separately from +7/−10.…”

“…They occur most commonly in IDH-wildtype gliomas with +7/−10 or EGFR amplification, yet these markers do not have complete overlap. TERT promoter mutations are associated with aggressive clinical behavior, even in some cases without +7/−10 or EGFR amplification [2, 8, 32, 33]. Therefore, if the clinical, radiologic and histopathologic features are definitive for a diffusely infiltrative astrocytic glioma, TERT promoter mutations can be considered as a marker for WHO grade IV behavior.…”