Renal cell carcinoma (RCC) is one of the leading causes of cancer mortality. Characterization of microRNA (miRNA) expression of RCC will help disclose new pathogenic pathways in tumourigenesis and progression and may lead to the development of molecular biomarkers and target-specific therapies for diagnosis, prognostication and treatment. With limitations in test specificity and the ability to detect novel miRNA and other small non-coding RNAs (smRNAs), microarray and RT-PCR techniques are being replaced by the evolving deep-sequencing technologies, at least in the discovery phase. Until now, cancer miRNA profiling of human benign and tumour specimen sets, using smRNA deep-sequencing (smRNA-seq), has not been reported. Specifically, due to concern over possible poor RNA quality/integrity, formalin-fixed paraffin-embedded (FFPE) samples have not been used for such studies. Here, we performed whole-genome smRNA-seq analysis using a benign and RCC specimen set and have successfully profiled the miRNA expression. Studies performed on paired frozen and FFPE specimens showed very similar results. Moreover, a comparison study of microarray, deep-sequencing and RT-PCR methodologies also showed a high correlation among the three technologies. To our knowledge, this is the first study to demonstrate that FFPE specimens can be used reliably for miRNA deep-sequencing analysis, making future large-scale clinical cohort/trial-based studies possible.

Renal cell carcinoma (RCC) metastasis portends a poor prognosis and cannot be reliably predicted. Early determination of the metastatic potential of RCC may help guide proper treatment. We analyzed microRNA (miRNA) expression in clear cell RCC (ccRCC) for the purpose of developing a miRNA expression signature to determine the risk of metastasis and prognosis. We used the microarray technology to profile miRNA expression of 78 benign kidney and ccRCC samples. Using 28 localized and metastatic ccRCC specimens as the training cohort and the univariate logistic regression and risk score methods, we developed a miRNA signature model in which the expression levels of miR-10b, miR-139-5p, miR-130b and miR-199b-5p were used to determine the status of ccRCC metastasis. We validated the signature in an independent 40-sample testing cohort of different stages of primary ccRCCs using the microarray data. Within the testing cohort patients who had at least 5 years follow-up if no metastasis developed, the signature showed a high sensitivity and specificity. The risk status was proven to be associated with the cancer-specific survival. Using the most stably expressed miRNA among benign and tumorous kidney tissue as the internal reference for normalization, we successfully converted his signature to be a quantitative PCR (qPCR)-based assay, which showed the same high sensitivity and specificity. The 4-miRNA is associated with ccRCC metastasis and prognosis. The signature is ready for and will benefit from further large clinical cohort validation and has the potential for clinical application.

Most cases of intravascular large cell lymphoma are of B-cell phenotype, with a few cases of T-cell lineage and rare cases with histiocytic features described. A definitive natural killer (NK) cell variant has not been recognized. This report is the first to describe the clinical, histologic, immunophenotypic, and molecular features of 2 cases of intravascular lymphoma with an NK cell phenotype (CD3epsilon+, CD2+, CD7+, CD56+, T-cell intracytoplasmic antigen-1+, perforin+, granzyme B+, CD20-, CD4-, CD5-, CD8-, T-cell receptor [TCR]betaF1-). Molecular studies for TCR gene rearrangements revealed a germline configuration. A 41-year-old man had erythematous plaque-like subcutaneous lesions of the lower extremities in which biopsy revealed Epstein-Barr virus-positive intravascular lymphoma. Following chemotherapy and stem cell transplantation, he was alive with no evidence of disease at 1 year. A 47-year-old woman had myalgias, arthralgias, weakness, fever, altered mental status, and pancytopenia. Bone marrow biopsy demonstrated intravascular lymphoma. Therapy was initiated; however, her condition deteriorated rapidly, and she died. Autopsy revealed involvement of multiple organs, including brain, kidneys, ovaries, and bone marrow. These cases represent the first documented examples of an NK cell variant of intravascular lymphoma.

The dopaminergic system in the brain seems to play an important role in the regulation of sexual behaviour. The relationship between genes for the D , D and D dopamine receptors and age at first sexual intercourse (AFSI) was examined in a sample of 414 non-Hispanic, European-American men and women. A significant association was observed between a DRD2 allele and AFSI and an even stronger association when the DRD2 allele was interacted with a DRD1 allele. A constrained regression model was constructed predicting AFSI using sex and a group of nine psychosocial variables as predictors. Adding the DRD2 and the DRD2-by-DRD1 predictors to this model increased the explained variance by 23 and 55%, respectively. Although these findings suggest a stronger association among males than among females, further research will be necessary to clarify this question, as well as to establish whether the observed association holds in other racial/ethnic groups.

Piwi-interacting RNAs (piRNAs) are a distinct group of small noncoding RNAs (sncRNAs) that silence transposable genetic elements to protect genome integrity. Because of their limited expression in gonads and sequence diversity, piRNAs remain the most mysterious class of small RNAs. Studies have shown piRNAs are present in somatic cells and dysregulated in gastric, breast and liver cancers. By deep sequencing 24 frozen benign kidney and clear cell renal cell carcinoma (ccRCC) specimens and using the publically available piRNA database, we found 26,991 piRNAs present in human kidney tissue. Among 920 piRNAs that had at least two copies in one specimen, 19 were differentially expressed in benign kidney and ccRCC tissues, and 46 were associated with metastasis. Among the metastasis-related piRNAs, we found three piRNAs (piR-32051, piR-39894 and piR-43607) to be derived from the same piRNA cluster at chromosome 17. We confirmed the three selected piRNAs not to be miRNAs or miRNA-like sncRNAs. We further validated the aberrant expression of the three piRNAs in a 68-case formalin-fixed and paraffin-embedded (FFPE) ccRCC tissue cohort and showed the upregulation of the three piRNAs to be highly associated with ccRCC metastasis, late clinical stage and poor cancer-specific survival.