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
Abstract
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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