World Health Organization grade II–III astrocytomas consist of genetically distinct tumor lineages

Abstract

Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II–III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR‐based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm‐loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (−10q) were detected in IDH wild‐type tumors. Kaplan–Meier estimates for progression‐free survival showed that the tumors with mutant IDH, −1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild‐type IDH, +7, or −10q. As tumors with +7 (IDH wild‐type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.

Whole-exome sequencing identifies germline mutation in TP53 and ATRX in a child with genomically aberrant AT/RT and her mother with anaplastic astrocytoma

“…The proportion of the TP53 germline variant reads was increased in the mother's tumor sample ( Fig. 2 A; Supplemental Table 1 ), suggesting copy-neutral loss of the wild-type variant, which is commonly observed in Grade II–III diffuse gliomas ( Hattori et al 2016 ). This was indeed the case according to the copy-number analysis that utilized both sequence coverage and heterozygous allele frequencies in the germline ( Fig.…”

Survival Associations Using Perfusion and Diffusion Magnetic Resonance Imaging in Patients With Histologic and Genetic Defined Diffuse Glioma World Health Organization Grades II and III

“…Histological grade, although suffering from inter-and intraobserver variability as well as tissues sampling error, especially in grade II and III tumors [6][7][8][9] is still recognized as an important characteristic for classification of CNS tumors. According to the new 2016 WHO classification, diffuse astrocytoma (WHO grade II) and anaplastic astrocytoma (WHO grade III) are now divided in two sub-categories depending on the mutation of the IDH family of genes (IDH1, IDH2): IDH-mutant and IDH-wildtype.…”

Application of diffusion tensor tractography in the surgical treatment of brain tumors located in functional areas

“…The patient improved with regard to sensory aphasia following surgery. Postoperative pathological analysis revealed that the tumor was an astrocytoma (using World Health Organisation grade II) (12).…”