PATZ1 Is Overexpressed in Pediatric Glial Tumors and Correlates with Worse Event-Free Survival in High-grade Gliomas.

Annalisa Passariello,Alia Zerbato,Maria Elena Errico,Mario Capasso,Maria Capasso,Vittoria Donofrio,Laura Cerchia,Manuela Maestrini,Monica Fedele

doi:10.3390/cancers11101537

Abstract

Glial tumors are the leading cause of cancer-related death and morbidity in children. Their diagnosis, mainly based on clinical and histopathological factors, is particularly challenging because of their high molecular heterogeneity. Thus, tumors with identical histotypes could result in variable biological behaviors and prognoses. The PATZ1 gene has been recently shown to be expressed in adult gliomas, including glioblastomas, where it correlates with the proneural subtype and with a better prognosis. Here, we analyzed the expression of PATZ1 in pediatric gliomas, first at mRNA level in a public database, and then at protein level, by immunohistochemistry, in a cohort of 52 glial brain tumors from young patients aged from 6 months to 16 years. As for adult tumors, we show that PATZ1 is enriched in glial tumors compared to the normal brain, where it correlates positively and negatively with a proneural and mesenchymal signature, respectively. Moreover, we show that PATZ1 is expressed at variable levels in our cohort of tumors. Higher expression was detected in high-grade than low-grade gliomas, suggesting a correlation with the malignancy. Among high-grade gliomas, higher levels of PATZ1 have consistently been found to correlate with worse event-free survival. Therefore, our study may imply new diagnostic opportunities for pediatric gliomas.

Highlights

Pediatric brain tumors (PBT) account for about 25% of childhood neoplasms and are the second most common pediatric cancer, ranking immediately behind leukemia, and have the highest mortality among pediatric cancers [1]
Cancers 2019, 11, 1537 tumors have been grouped into low-grade and high-grade gliomas
The identification of these alterations is important for the therapeutic plan, as the presence of the K27M variant is the defining event for the newly recognized World Health Organization (WHO) entity, termed Diffuse Midline Glioma H3 K27M-mutant, WHO Grade IV, associated with a poor prognosis regardless of histological grade [7]

Summary

Introduction

Pediatric brain tumors (PBT) account for about 25% of childhood neoplasms and are the second most common pediatric cancer, ranking immediately behind leukemia, and have the highest mortality among pediatric cancers [1]. Pediatric gliomas are characterized by gene amplifications, deletions, and other types of mutations, distinct from the adult counterpart; the most common alterations in pLGG are BRAF mutations, followed by FGFR1 alterations; in pHGG, TP53 and H3F3A mutations dominate the genomic landscape. Mutations at K27 and G34 amino acid residues of the H3F3A gene are the most significant findings in pHGG, whereas they are rare in adult HGG The identification of these alterations is important for the therapeutic plan, as the presence of the K27M variant is the defining event for the newly recognized WHO entity, termed Diffuse Midline Glioma H3 K27M-mutant, WHO Grade IV, associated with a poor prognosis regardless of histological grade [7]

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