Molecular Markers for Prostate Cancer Risk Stratification from Multiple Ultrasound-Guided Biopsies.

摘要

The hypothesis underlying this Idea Grant project was that if it were possible to isolate and genomically analyze hundreds of single cells from prostate cancer (PCa) biopsies, that it would then be possible to create an objective diagnostic and prognostic molecular measure of primary prostate cancer that provide new insight into treating the disease. The first goal was to develop a protocol for isolating single cells from fresh biopsies that was consistent with, and not disruptive to standard histopathology procedures. We achieved this goal within the first 8 months of the project. We then proceeded to analyze 10 cases ranging from benign and high grade pre-invasive prostate cancers to intermediate level cancers scored as Gleason 6 and 7 by histopathology. We analyzed a total of over 3600 single cells from multiple biopsies of these ten cases. Our conclusions are first, that molecular measures of cancer development measured by the establishment of clonal lineages of genomically rearranged cancer cells in the prostate, as measured by copy number variation (CNV) profiles can be used to identify the earliest stages of invasive cancer; and second, that the degree of clonal development measured by CNV is directly correlated with Gleason Score. These results lead us to believe that this line of investigation should be extended to deeper DNA sequencing on a clinically relevant number of cases in order to establish prognostic molecular biomarkers for PCa.