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Copy-Number Alterations in the Colorectal Cancer Genome

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Molecular Pathogenesis of Colorectal Cancer

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Abstract

Colorectal cancer (CRC) has classically been divided into two main genetic/molecular subtypes; tumors characterized by chromosomal instability (CIN) and those with microsatellite instability (MSI). Although cases with MSI often have relatively bland copy-number profiles, cases characterized by CIN typically possess many somatic copy-number alterations (SCNAs). Thanks to the remarkable progress in copy-number profiling techniques with both increased resolution and sample throughput, the landscape of the SCNAs in CRC has increasingly begun to be revealed. Many of the arm-level SCNAs of CRC are shared by many epithelial cancers but some of them are unique to gut epithelial cancers or to CRC. Gain of 8q, 20p/q and loss of 17p are commonly observed across the gut adenocarcinomas. More unique to CRC are highly recurrent chromosomal gains of 13q. Important focal SCNAs include the amplifications of 8q at MYC, 20q around BCL2L1, 11p at IGF2, and miR-483, and 17q at ERBB2. The amplification of ERBB2 is particularly important because it is clinically targetable. Focal loss of tumor suppressor genes such as TP53 and SMAD4 reflects the selective advantage of loss of these factors. Although we began to reveal the landscape of SCNA in CRC, we have yet to fully appreciate the biologic rationale and significance for this spectrum of recurrent structural alterations in the genomes of these cancers.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Jihun Kim & Adam J. Bass

  2. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

    Jihun Kim

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  1. Jihun Kim
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  2. Adam J. Bass
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Correspondence to Adam J. Bass .

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Editors and Affiliations

  1. Molecular Pathology Unit, Harvard Medical School, Charlestown, Massachusetts, USA

    Kevin M. Haigis, Ph.D.

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Kim, J., Bass, A.J. (2013). Copy-Number Alterations in the Colorectal Cancer Genome. In: Haigis, Ph.D., K. (eds) Molecular Pathogenesis of Colorectal Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8412-7_10

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