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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.Significance: 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. Cancer Res; 78(2); 348-58. Ó2017 AACR.

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The HML and HMR loci carry unexpressed copies of MAT  a and MATα information, and a replica of that information is transposed to MAT during mating-type interchange in Saccharomyces yeasts. A negative control mechanism keeps silent the information located at the HML and HMR loci. We mapped these loci by constructing strains in which these loci are expressed. In these strains, the mating type of the segregants is dependent upon the allele at HML and HMR. This novel approach is independent of their switching function. HML is located on the left arm of chromosome III distal to his4 by about 26.8 centimorgans (cM). HMR maps on the right arm of the same chromosome distal to thr4 by about 39.8 cM and proximal to MAL2 by about 1.0 cM. The results allow the exact placement of these loci and are in accord with the observations made by Harashima and Oshima (1976).

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<p>A zipped file archive containing Supplementary Table 3 as an Excel spreadsheet and a subfolder with graphic images pointed to by the hyperlinks in the spreadsheet.</p>