Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma

Abstract

Gain of 1q is one of the most common alterations in cancer and has been associated with adverse clinical behaviour in ependymoma. The aim of this study was to investigate this region to gain insight into the role of 1q genes in intracranial paediatric ependymoma. To address this issue we generated profiles of eleven ependymoma, including two relapse pairs and seven primary tumours, using comparative genome hybridisation and serial analysis of gene expression. Analysis of 656 SAGE tags mapping to 1q identified CHI3L1 and S100A10 as the most upregulated genes in the relapse pair with de novo 1q gain upon recurrence. Moreover, three more members of the S100 family had distinct gene expression profiles in ependymoma. Candidates (CHI3L1, S100A10, S100A4, S100A6 and S100A2) were validated using immunohistochemistry on a tissue microarray of 74 paediatric ependymoma. In necrotic cases, CHI3L1 demonstrated a distinct staining pattern in tumour cells adjacent to the areas of necrosis. S100A6 significantly correlated with supratentorial tumours (Po0.001) and S100A4 with patients under the age of 3 years at diagnosis (P ¼ 0.038). In conclusion, this study provides evidence that S100A6 and S100A4 are differentially expressed in clinically relevant subgroups, and also demonstrates a link between CHI3L1 protein expression and necrosis in intracranial paediatric ependymoma.

Histology and Molecular Pathology of Pediatric Brain Tumors

“…Oncogene amplifications are infrequent in ependymomas, and only single cases harbor the homozygous deletion of the CDKN2A/B gene. 30 Importantly, the gain of chromosome 1q is a common finding in several studies associated with poor prognosis 27,28,31 (Figure 2C, D). In contrast to this, a better prognosis has been associated with the loss of 6q25.3 in patients with anaplastic ependymomas.…”

Somatic gene copy number alterations in colorectal cancer: new quest for cancer drivers and biomarkers

“…In addition, copy number gain of the S100 family seems to be associated with varies cancers, including CRC. 93,94 The PRKAB2 gene located on 1q21.1 is also frequently deleted in CRC, especially when TP53 has no mutation. Mechanistically, PRLAB2 encodes a protein that controls AMPK (AMP-activated protein kinase) under the regulation of p53.…”

Pediatric Ependymoma: Biological Perspectives

“…GAC1 amplification has already been implicated in the pathogenesis of malignant gliomas (148). CHI3L1 upregulation may be involved in pediatric intracranial ependymoma recurrence, whereas its corresponding protein expression has been correlated with tumor necrosis (147). These genes and the locus 1q25 merit further investigation with high resolution genomic techniques and gene expression studies that analyze larger numbers of pediatric ependymomas as an independent cohort.…”