Utility of single cell genomics in diagnostic evaluation of prostate cancer

Alexander, J., Kendall, J., McIndoo, J., Rodgers, L., Aboukhalil, R., Levy, D., Stepansky, A., Sun, G., Chobadjiev, L., Riggs, M., Cox, H., Hakker, I., Nowak, D. G., Laze, J., Llukani, E., Srivastava, A., Gruschow, S., Yadav, S. S., Robinson, B. D., Atwal, G., Trotman, L. C., Lepor, H., Hicks, J. B., Wigler, M., Krasnitz, A. (January 2018) Utility of single cell genomics in diagnostic evaluation of prostate cancer. Cancer Res, 78 (2). pp. 348-358. ISSN 0008-5472

URL: https://www.ncbi.nlm.nih.gov/pubmed/29180472
DOI: 10.1158/0008-5472.can-17-1138


A distinction between indolent and aggressive disease is a major challenge in diagnostics of prostate cancer. As genetic heterogeneity and complexity may influence clinical outcome, we have initiated studies on single tumor cell genomics. In this study, we demonstrate that sparse DNA sequencing of single cell nuclei from prostate core biopsies is a rich source of quantitative parameters for evaluating neoplastic growth and aggressiveness. These include the presence of clonal populations, the phylogenetic structure of those populations, the degree of the complexity of copy number changes in those populations, and measures of the proportion of cells with clonal copy number signatures. The parameters all showed good correlation to the measure of prostatic malignancy, the Gleason score, derived from individual prostate biopsy tissue cores. Remarkably, a more accurate histopathological measure of malignancy, the surgical Gleason score, agrees better with these genomic parameters of diagnostic biopsy than it does with the diagnostic Gleason score and related measures of diagnostic histopathology. This is highly relevant since primary treatment decisions are dependent upon the biopsy and not the surgical specimen. Thus, single cell analysis has the potential to augment traditional core histopathology, improving both the objectivity and accuracy of risk assessment and inform treatment decisions.

Item Type: Paper
Subjects: diseases & disorders
Investigative techniques and equipment
diseases & disorders > neoplasms
Investigative techniques and equipment > assays
Investigative techniques and equipment > biomarker
diseases & disorders > cancer > cancer types > prostate cancer
Investigative techniques and equipment > assays > Single cell sequencing
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Program > Signal Transduction
CSHL labs > Atwal lab
CSHL labs > Krasnitz lab
CSHL labs > Levy lab
CSHL labs > Trotman lab
CSHL labs > Wigler lab
School of Biological Sciences > Publications
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User: Matt Covey
Date: 15 January 2018
Date Deposited: 01 Dec 2017 22:14
Last Modified: 06 Feb 2024 20:50
PMCID: PMC5771881
Related URLs:
URI: https://repository.cshl.edu/id/eprint/35676

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