ETV/Pea3 family transcription factor‐encoding genes are overexpressed in CIC‐mutant oligodendrogliomas. Issue 12 (10th September 2015)

• Record Type: Journal Article
• Authors: Padul, Vijay; Epari, Sridhar; Moiyadi, Aliasgar; Shetty, Prakash; Shirsat, Neelam Vishwanath
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 12(2015:Dec.)
• Page Start: 725
• Page End: 733
• Publication Date: 2015-09-10
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22283
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Oligodendrogliomas with combined loss of chromosome arms 1p and 19q are known to be particularly sensitive to chemotherapy, and the <italic>CIC</italic> gene located on 19q is known to be mutated in over 50% of the 1p/19q codeleted oligodendrogliomas. However, the role of <italic>CIC</italic> in the oligodendroglioma pathogenesis is not known. Exome sequencing of 11 oligodendroglial tumors identified 9 tumors with combined loss of 1p and 19q. Somatic mutations were found in the <italic>CIC</italic> and <italic>FUBP1</italic> genes. Recurrent somatic mutations were also identified in the Notch signaling pathway genes <italic>NOTCH1</italic> and <italic>MAML3</italic>, the chromatin modifying gene <italic>ARID1A</italic> and in <italic>KRAS</italic>. Comparison of the transcriptome profiles of <italic>CIC</italic>‐mutant and <italic>CIC</italic>‐wild type oligodendrogliomas from the study cohort as well as 65 1p/19q codeleted oligodendrogliomas from the TCGA cohort identified genes encoding the ETV transcription factor family to be significantly upregulated in the <italic>CIC</italic>‐mutant tumors. Upregulation of a number of negative regulators of the receptor tyrosine kinase signaling pathway like Sprouty and SPRED family members in the <italic>CIC</italic>‐mutant oligodendrogliomas is likely due to the constitutive activation of the pathway resulting from inactive CIC protein. Higher expression of the oncogenic ETV transcription factors in the <italic>CIC</italic>‐mutant oligodendrogliomas may make these tumors more aggressive than the CIC‐wild type tumors. © 2015 Wiley Periodicals, Inc.</p> </abstract>