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CIC Mutation as Signature Alteration in Oligodendroglioma

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Next Generation Sequencing in Cancer Research, Volume 2

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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.

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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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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada, T2N 4N1

    Shiekh Tanveer Ahmad & Wei Wu

  2. Department of Pathology and Laboratory Medicine, Southern Alberta Cancer Research Institute, University of Calgary, Room HRIC 2A-08, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1

    Jennifer A. Chan

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  1. Shiekh Tanveer Ahmad
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  2. Wei Wu
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  3. Jennifer A. Chan
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Correspondence to Jennifer A. Chan .

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Editors and Affiliations

  1. Department of Pathology and Laboratory, Medicine, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada

    Wei Wu

  2. Faculty of Science, Biochemistry Department, Center of Innovation in Personalized Medicine, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia

    Hani Choudhry

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Ahmad, S.T., Wu, W., Chan, J.A. (2015). CIC Mutation as Signature Alteration in Oligodendroglioma. In: Wu, W., Choudhry, H. (eds) Next Generation Sequencing in Cancer Research, Volume 2. Springer, Cham. https://doi.org/10.1007/978-3-319-15811-2_24

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