title: ETV/Pea3 family transcription factor-encoding genes are overexpressed in CIC-mutant oligodendrogliomas.
abstract: Oligodendrogliomas with combined loss of chromosome arms 1p and 19q are known to be particularly sensitive to chemotherapy, and the CIC gene located on 19q is known to be mutated in over 50% of the 1p/19q codeleted oligodendrogliomas. However, the role of CIC 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 CIC and FUBP1 genes. Recurrent somatic mutations were also identified in the Notch signaling pathway genes NOTCH1 and MAML3, the chromatin modifying gene ARID1A and in KRAS. Comparison of the transcriptome profiles of CIC-mutant and CIC-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 CIC-mutant tumors. Upregulation of a number of negative regulators of the receptor tyrosine kinase signaling pathway like Sprouty and SPRED family members in the CIC-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 CIC-mutant oligodendrogliomas may make these tumors more aggressive than the CIC-wild type tumors.
authors.affiliation: Shirsat Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Padul
authors.affiliation: Department of Pathology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Epari
authors.affiliation: Neurosurgery Services, Department of Surgical Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Aliasgar
authors.initials: A
authors.lastname: Moiyadi
authors.affiliation: Neurosurgery Services, Department of Surgical Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Shetty
authors.affiliation: Shirsat Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Neelam Vishwanath
authors.initials: NV
authors.lastname: Shirsat
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D009837:Oligodendroglioma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C112476:ARID1A protein, human; D017500:Adenovirus E1A Proteins; C498610:CIC protein, human; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C079853:ETV4 protein, human; C086680:ETV5 protein, human; C492258:FUBP1 protein, human; C117307:KRAS protein, human; C471298:MAML3 protein, human; C497761:NOTCH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D007521:Isocitrate Dehydrogenase; D004265:DNA Helicases; D016283:Proto-Oncogene Proteins p21(ras)