CIC Mutation as Signature Alteration in Oligodendroglioma

Chapter

Abstract

Oligodendroglioma (ODG) is a type brain tumor that predominantly affects young adults and that is characterized by unique clinical, morphological, genetic, and molecular features. Molecular characterization of ODGs has identified concurrent 1p and 19q whole-arm chromosomal losses and IDH mutations as signature alterations in ODG. More recently, mutations in the gene CIC on chromosome 19q13.2 have been found to be present in the majority of ODGs. CIC mutations occur nearly exclusively in the context of 1p/19q co-deletion, and it is likely that the CIC mutation on the remaining 19q allele is integral to the disease pathogenesis. In contrast to ODGs, where >70 % of cases harbor CIC mutations, CIC mutations are found at a low frequency across diverse tumor types. To date, little is known how CIC mutation contributes to development of ODGs or other cancers. Most of literature on CIC has been based on studies in Drosophila, where CIC has spatiotemporal effects in regulating RTK signaling for normal embryonic development. In this chapter, we provide a brief introduction to oligodendrogliomas, review CIC’s role as a transcriptional repressor and functions in development, and discuss the potential role(s) of CIC mutation in the pathogenesis of human cancer.

Keywords

CIC RTK ODG Neurodevelopment PEA3 ETS 1p/19q IDH 

Abbreviations

CIC

Capicua

CP

Cortical plate

EGFR

Epidermal growth factor receptor

ETS

E twenty-six

ETV

ETS translocation variant

HMG

High mobility group

IDH

Isocitrate dehydrogenase

IZ

Intermediate zone

MMP

Metallomatrix protein

NSC

Neural stem cell

ODG

Oligodendroglioma

OPC

Oligodendrocyte precursor cell

PDGFR

Platelet derived growth factor receptor

PEA3

Polyoma enhancer activator 3

PTEN

Phosphatase and tensin homolog

RTK

Receptor tyrosine kinase

SVZ

Subventricular zone

VZ

Ventricular zone

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Shiekh Tanveer Ahmad
    • 1
  • Wei Wu
    • 1
  • Jennifer A. Chan
    • 2
  1. 1.Department of Pathology and Laboratory Medicine, Southern Alberta Cancer Research InstituteUniversity of CalgaryCalgaryCanada
  2. 2.Department of Pathology and Laboratory Medicine, Southern Alberta Cancer Research InstituteUniversity of CalgaryCalgaryCanada

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