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Integrating the multiple dimensions of genomic and epigenomic landscapes of cancer

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Abstract

Advances in high-throughput, genome-wide profiling technologies have allowed for an unprecedented view of the cancer genome landscape. Specifically, high-density microarrays and sequencing-based strategies have been widely utilized to identify genetic (such as gene dosage, allelic status, and mutations in gene sequence) and epigenetic (such as DNA methylation, histone modification, and microRNA) aberrations in cancer. Although the application of these profiling technologies in unidimensional analyses has been instrumental in cancer gene discovery, genes affected by low-frequency events are often overlooked. The integrative approach of analyzing parallel dimensions has enabled the identification of (a) genes that are often disrupted by multiple mechanisms but at low frequencies by any one mechanism and (b) pathways that are often disrupted at multiple components but at low frequencies at individual components. These benefits of using an integrative approach illustrate the concept that the whole is greater than the sum of its parts. As efforts have now turned toward parallel and integrative multidimensional approaches for studying the cancer genome landscape in hopes of obtaining a more insightful understanding of the key genes and pathways driving cancer cells, this review describes key findings disseminating from such high-throughput, integrative analyses, including contributions to our understanding of causative genetic events in cancer cell biology.

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Abbreviations

CGH:

Comparative genomic hybridization

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Acknowledgments

This work was supported by funds from the Canadian Institutes for Health Research (MOP 86731, MOP 77903), Canadian Cancer Society (CCS20485), NCI Early Detection Research Network (EDRN; 5U01 CA84971-10), and the Canary Foundation. CEA was supported by the United States National Institutes of Health (HG004663). RC, KLT, WWL, and IMW are supported by scholarships from the Canadian Institutes for Health Research and the Michael Smith Foundation for Heath Research.

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Authors and Affiliations

  1. Genetics Unit - Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada

    Raj Chari, Kelsie L. Thu, Ian M. Wilson, William W. Lockwood, Kim M. Lonergan, Bradley P. Coe, Chad A. Malloff, Cathie Garnis & Wan L. Lam

  2. Interdisciplinary Oncology Program, University of British Columbia, Vancouver, BC, Canada

    Kelsie L. Thu & Wan L. Lam

  3. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Adi F. Gazdar

  4. Imaging Unit - Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada

    Stephen Lam & Calum E. MacAulay

  5. Center for Molecular and Human Genetics, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    Carlos E. Alvarez

  6. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    Carlos E. Alvarez

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  1. Raj Chari
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Correspondence to Raj Chari.

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Carlos E. Alvarez and Wan L. Lam contributed equally.

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Chari, R., Thu, K.L., Wilson, I.M. et al. Integrating the multiple dimensions of genomic and epigenomic landscapes of cancer. Cancer Metastasis Rev 29, 73–93 (2010). https://doi.org/10.1007/s10555-010-9199-2

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