Ovarian cancer is the most deadly gynecological cancer. The high rate of mortality is due to the large tumor burden with extensive metastatic lesion of the abdominal cavity. Despite initial chemosensitivity and improved surgical procedures, abdominal recurrence remains an issue and results in patients' poor prognosis. Transcriptomic and genetic studies have revealed significant genome pathologies in the primary tumors and yielded important information regarding carcinogenesis. There are, however, few studies on genetic alterations and their consequences in peritoneal metastatic tumors when compared to their matched ovarian primary tumors. We used high-density SNP arrays to investigate copy number variations in matched primary and metastatic ovarian cancer from 9 patients. Here we show that copy number variations acquired by ovarian tumors are significantly different between matched primary and metastatic tumors and these are likely due to different functional requirements. We show that these copy number variations clearly differentially affect specific pathways including the JAK/STAT and cytokine signaling pathways. While many have shown complex involvement of cytokines in the ovarian cancer environment we provide evidence that ovarian tumors have specific copy number variation differences in many of these genes.

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Research Question. Long non-coding RNAs (lncRNAs) do not show protein translation but do have gene regulatory functions in several disease states. Studies have shown that lncRNA differ in overweight PCOS women with increased insulin resistance and hyperandrogenemia.The objective of this study was to determine lncRNA in serum in age and weight matched non-obese women with and without PCOS. MethodsIn this prospective pilot cohort study, lncRNA was measured in serum in 13 non-obese women with PCOS and 10 control women undergoing IVF.Results. There was no difference between groups for age, BMI or insulin resistance; PCOS women showed a higher free androgen index (p=0.03) and AMH (p=0.001). A total of 29 lncRNA (p<0.05) differed between PCOS groups. LncRNA AC095350.1 correlated with age (r=0.79, p<0.05), but there was no correlation seen between the significantly different lncRNA and free androgen index (FAI) or anti-mullerian hormone (AMH). Functional pathway assessment through the Ingenuity Pathway Assessment (IPA) tool showed no relationships for the lncRNA. Conclusion.LncRNA in serum differed between non-obese PCOS and control women and the pattern of expression differed to that reported in obese PCOS from the same ethnic population but did not correlate with androgen or insulin resistance.

Kidney transplantation is the treatment of choice for patients with end-stage kidney failure, but transplanted allograft could be affected by viral and bacterial infections and by immune rejection. The standard test for the diagnosis of acute pathologies in kidney transplants is kidney biopsy. However, noninvasive tests would be desirable. Various methods using different techniques have been developed by the transplantation community. But these methods require improvements. We present here a cost-effective method for kidney rejection diagnosis that estimates donor/recipient-specific DNA fraction in recipient urine by sequencing urinary cell DNA. We hypothesized that in the no-pathology stage, the largest tissue types present in recipient urine are donor kidney cells, and in case of rejection, a larger number of recipient immune cells would be observed. Extensive in-silico simulation was used to tune the sequencing parameters: number of variants and depth of coverage. Sequencing of DNA mixture from 2 healthy individuals showed the method is highly predictive (maximum error < 0.04). We then demonstrated the insignificant impact of familial relationship and ethnicity using an in-house and public database. Lastly, we performed deep DNA sequencing of urinary cell pellets from 32 biopsy-matched samples representing two pathology groups: acute rejection (AR, 11 samples) and acute tubular injury (ATI, 12 samples) and 9 samples with no pathology. We found a significant association between the donor/recipient-specific DNA fraction in the two pathology groups compared to no pathology (P = 0.0064 for AR and P = 0.026 for ATI). We conclude that deep DNA sequencing of urinary cells from kidney allograft recipients offers a noninvasive means of diagnosing acute pathologies in the human kidney allograft.

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