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SPORE in Prostate Cancer

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Utility of Single-Cell Genomics in Diagnostic Evaluation of Prostate Cancer.

TitleUtility of Single-Cell Genomics in Diagnostic Evaluation of Prostate Cancer.
Publication TypeJournal Article
Year of Publication2018
AuthorsAlexander J, Kendall J, McIndoo J, Rodgers L, Aboukhalil R, Levy D, Stepansky A, Sun G, Chobardjiev L, Riggs M, Cox H, Hakker I, Nowak DG, Laze J, Llukani E, Srivastava A, Gruschow S, Yadav SS, Robinson B, Atwal G, Trotman LC, Lepor H, Hicks J, Wigler M, Krasnitz A
JournalCancer Res
Volume78
Issue2
Pagination348-358
Date Published2018 01 15
ISSN1538-7445
KeywordsAged, Aged, 80 and over, Biomarkers, Tumor, Genomics, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Phylogeny, Prostatectomy, Prostatic Neoplasms, Risk Assessment, Single-Cell Analysis
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 histopathologic 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 because 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. Genomic analysis of multiple individual cells harvested from prostate biopsies provides an indepth view of cell populations comprising a prostate neoplasm, yielding novel genomic measures with the potential to improve the accuracy of diagnosis and prognosis in prostate cancer. .

DOI10.1158/0008-5472.CAN-17-1138
Alternate JournalCancer Res.
PubMed ID29180472
PubMed Central IDPMC5771881
Grant ListT32 GM065094 / GM / NIGMS NIH HHS / United States
R01 CA137050 / CA / NCI NIH HHS / United States
U01 CA188590 / CA / NCI NIH HHS / United States
P30 CA045508 / CA / NCI NIH HHS / United States
S10 OD020122 / OD / NIH HHS / United States