Utility of single cell genomics in diagnostic evaluation of prostate cancer. - PubMed - NCBI
Cancer Res. 2017 Nov 27. pii: canres.1138.2017. doi: 10.1158/0008-5472.CAN-17-1138. [Epub ahead of print]
Utility of single cell genomics in diagnostic evaluation of prostate cancer.
Alexander J1,
Kendall J2,
McIndoo J1,
Rodgers L3,
Aboukhalil R4,
Levy D3,
Stepansky A5,
Sun G6,
Chobadjiev L7,
Riggs M3,
Cox H3,
Hakker I3,
Nowak DG3,
Laze J8,
Llukani E8,
Srivastava A9,
Gruschow S10,
Yadav SS11,
Robinson BD12,
Atwal G13,
Trotman LC3,
Lepor H14,
Hicks JB15,
Wigler M16,
Krasnitz A17.
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.
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