Integrated genomic and transcriptomic analysis suggests KRT18 mutation and MTAP are key genetic alterations related to the prognosis between astrocytoma and glioblastoma.

Abstract

Background\nAstrocytoma and glioblastoma (GBM) are the two main subtypes of glioma, with the 2016 World Health Organization Classification of Tumors of the Central Nervous System (CNS WHO) classifying them into different grades. GBM is the most malignant among all CNS tumors with a 5-year survival rate of less than 5%. Although the prognosis of patients with astrocytoma is better than that of GBM in general, patients with anaplastic astrocytoma (AA) and isocitrate dehydrogenase (IDH) wild type have a similar prognosis as GBM and entail a high risk of progression. Exploring the molecular driving force behind the malignant phenotype of astrocytoma and GBM will help explain the diversity of glioma and discover new drug targets.\n\n\nMethods\nWe enrolled 12 patients with astrocytoma and 12 patients with GBM and performed whole-exome sequencing (WES) and RNA sequencing analysis on tumor samples from the patients.\n\n\nResults\nWe found that the somatic mutation of KRT18, which is associated with cell apoptosis and adhesion by interacting with receptor 1-associated protein (TRADD) and pinin, was significantly enriched in astrocytoma, but rare in GBM. Copy number loss of MTAP, which is closely related to a poor prognosis of glioma, was found to be significantly enriched in GBM. In addition, different somatic copy number alteration (SCNA), gene expression, and immune cell infiltration patterns between astrocytoma and GBM were found.\n\n\nConclusions\nThis study revealed the distinct characteristics of astrocytoma and GBM at the DNA and RNA level. Somatic mutation of KRT18 and copy number loss of MTAP, two key genetic alterative genes in astrocytoma and GBM, have the potential to become therapeutic targets in glioma.