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Circulating Tumor-Related DNA Alterations as Prostate Cancer Biomarkers

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Circulating Nucleic Acids in Plasma and Serum

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Abstract

Although most prostate cancers are now detected at an early stage, it is still difficult to differentiate between indolent and aggressive disease. Prostate cancer biomarkers are thus desperately needed to complement current clinical factors in the identification and monitoring of aggressive disease. Promising biomarkers include the detection and analysis of cell-free circulating DNA alterations in the blood of prostate cancer patients. This approach is minimally invasive, cost effective, and can allow serial monitoring of disease progression and therapy. Moreover, genetic and epigenetic alterations in cell-free DNA may reflect the biology of the tumor, and eventually provide clues about the aggressiveness of the disease. Allelic imbalance or DNA hypermethylation analyses have both shown to specifically detect prostate cancer with variable sensitivity. However, by combining both approaches, we have found that we can significantly improve the sensitivity of prostate cancer detection. These findings support the use of multimarker circulating DNA assays to detect prostate cancer, and justify further investigation to identify specific multimarker combinations associated with prostate cancer progression.

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Abbreviations

AI:

Allelic imbalance

BPH:

Benign prostatic hyperplasia

CTC:

Circulating tumor cell

LOH:

Loss of heterozygosity

MSP:

Methylation-specific PCR

PCa:

Prostate cancer

PCSM:

Prostate cancer-specific mortality

PIN:

Prostatic intraepithelial neoplasia

PSA:

Prostate-specific antigen

PSADT:

PSA doubling time

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Acknowledgements

We thank members of the Molecular Oncology Department at the John Wayne Cancer Institute for their technical support. L.L. is a recipient of a Canadian Institutes of Health Research (CIHR) fellowship award. This work was supported by a US Department of Defense prostate grant award number DAMD17-03-0261 and the Associates for Breast and Prostate Cancer Studies (Beverly Hills, CA).

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Authors and Affiliations

  1. Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA

    Laurent Lessard, Eiji Sumami & Dave S.B. Hoon

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  1. Laurent Lessard
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  2. Eiji Sumami
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  3. Dave S.B. Hoon
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Correspondence to Dave S.B. Hoon .

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  1. , Anatomy & Human Sciences, King's College London, London Bridge, London, SE1 1UL, United Kingdom

    Peter B. Gahan

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Lessard, L., Sumami, E., Hoon, D.S. (2010). Circulating Tumor-Related DNA Alterations as Prostate Cancer Biomarkers. In: Gahan, P. (eds) Circulating Nucleic Acids in Plasma and Serum. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9382-0_3

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