A new mammal skull from the Lower Cretaceous of China with implications for the evolution of obtuse-angled molars and 'amphilestid' eutriconodonts.

We report the discovery of Juchilestes liaoningensis, a new genus and species of eutriconodont mammal from the Lujiatun Site of the Lower Cretaceous Yixian Formation (123.2 +/- 1.0 Ma; Lower Aptian). The holotype preserves a partial skull and full dentition. Among eutriconodonts, its lower dentition is similar to taxa formerly assigned to the paraphyletic group of 'amphilestids'. Some have considered 'amphilestid' molars to represent the structural intermediate between the lower molars of the 'triconodont' pattern of cusps in alignment and the fully triangulate and more derived therian molars. However, 'amphilestid' taxa were previously represented only by the lower dentition. Our study reveals, for the first time, the upper dentition and skull structure of an 'amphilestid', and shows that at least some eutriconodonts have an obtuse-angled cusp pattern on molars in middle positions of the long molar series. Its petrosal is similar to those of other eutriconodonts and spalacotheroid 'symmetrodonts'. Our phylogenetic analyses suggest that (i) Juchilestes is most closely related to the Early Cretaceous Hakusanodon from Japan, in the same Eastern Asiatic geographic region; (ii) 'amphilestids' are not monophyletic; and (iii) eutriconodonts might not be a monophyletic group, although this hypothesis must be further tested.

Mapping of TMPRSS2-ERG fusions in the context of multi-focal prostate cancer.

TMPRSS2-ERG gene fusion leading to the androgenic induction of the ERG proto-oncogene expression is a highly prevalent oncogenic alteration in prostate tumor cells. Prostate cancer is a multi-focal disease, and the origins as well as biological contribution of multiple cancer foci remain unclear with respect to prostate cancer onset or progression. To assess the role of TMPRSS2-ERG alteration in prostate cancer onset and/or progression, we have evaluated the status of fusion transcripts in benign glands, prostatic intraepithelial neoplasia (PIN) and multiple cancer foci of each prostate. Quantitative expression of TMPRSS2-ERG fusion type A and C transcripts was analyzed in benign, tumor and PIN areas, selected from whole-mount radical prostatectomy slides. TMPRSS2-ERG expression was correlated with clinicopathological features. Overall, 30 of 45 (67%) patients exhibited TMPRSS2-ERG fusion transcripts in at least one tumor focus. Of 80 tumor foci analyzed, 39 had TMPRSS2-ERG fusion (type A only: 30, type C only: 2, both types A and C: 7), with predominant detection of the TMPRSS2-ERG fusion type A (27/30, 90%) in the index tumors. Of 14 PIN lesions, 2 were positive for type A fusion. Frequent presence of the TMPRSS2-ERG in index tumors suggests critical roles of ERG alterations in the onset and progression of a large subset of prostate cancer. However, heterogeneity of the TMPRSS2-ERG detection in the context of multiple cancer foci and its frequency in PIN also support the role of other genomic alterations in the origins of prostate cancer.

Diagnostic potential of prostate-specific antigen expressing epithelial cells in blood of prostate cancer patients.

PURPOSE: Prostate-specific antigen (PSA) test has become a widely used screening test in prostate cancer (CaP). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of CaP-specific diagnostic and prognostic markers is needed. Detection of circulating PSA-expressing cells (CPECs) in blood and bone marrow of CaP patients has potential in molecular diagnosis and prognosis. Our novel observations of the frequent presence of CPECs in CaP patients with organ-confined disease by reverse transcription (RT)-PCR-PSA assay in epithelial cells enriched from peripheral blood (ERT-PCR/PSA) have led us to test the hypothesis that CPECs have diagnostic potential for CaP. EXPERIMENTAL DESIGN: Epithelial cells from peripheral blood of radical prostatectomy patients or prostate biopsy patients were isolated using antiepithelial cell antibody, Ber-EP4-coated magnetic beads, and total RNA specimens from these cells were analyzed for PSA expression by RT-PCR. RESULTS: Peripheral blood specimens of 108 of 135 (80.0%) CaP patients were positive in ERT-PCR/PSA assay. Peripheral blood specimens from 45 control men were virtually negative (97.8%). In the blinded investigation, 84 patients who had biopsy for suspicion of CaP were evaluated by ERT-PCR/PSA assay. Eighteen of 22 (81.8%) patients with biopsy-proven CaP were positive, and 54 of 62 (87.1%) patients with biopsy negative for CaP were negative in this assay (P < 0.001). CONCLUSIONS: Our study provides intriguing novel results showing that the majority of patients with clinically organ-confined CaP contain CPECs. Strong concordance between the biopsy results and ERT-PCR/PSA assay (sensitivity 81.8%; specificity 87.1%) suggests a potentially new diagnostic application of this type of assay in CaP diagnosis.