Citations

AbstractStudying signal transduction in skin‐resident T cells (sr‐T cells) can be limited by the small size of clinical biopsies. Here, we isolated sr‐T cells from clinical samples and analysed signalling protein complexes by multiplex immunoprecipitation detected by flow cytometry (mIP‐FCM). In samples from two independent donors, antigenic stimulation induced signalling proteins to join shared complexes that were observed in seven pairwise combinations among five proteins. This demonstrates that sr‐T cells isolated from small clinical samples provide sufficient material for mIP‐FCM‐based analysis of signalling‐induced protein complexes. We propose that this strategy may be useful for gaining improved mechanistic insight of sr‐T cell signal transduction associated with dermatological disease.

AbstractWe provide a mini‐review of how biobanks can support clinical genetics in the era of personalized medicine. We discuss types of biobanks, including disease specific and general biobanks not focused on one disease. We present considerations in setting up a biobank, including consenting and governance, biospecimens, risk factor and related data, informatics, and linkage to electronic health records for phenotyping. We also discuss the uses of biobanks and ongoing considerations, including genotype‐driven recruitment, investigations of gene–environment associations, and the re‐use of data generated from studies. Finally, we present a brief discussion of some of the unresolved issues, such as return of research results and sustaining biobanks over time. In summary, carefully designed biobanks can provide critical research and infrastructure support for clinical genetics in the era of personalized medicine.

BACKGROUNDSince 2002, priority Model for End‐stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long‐term survival rates among patients with HCC tumors meeting the Milan criteria in the post‐MELD exception era.METHODSThe current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database.RESULTSA total of 43% of patients did not receive any specific therapy. Overall, the 5‐year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%‐27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%‐82%). Long‐term survival was found to be dependent on age, race/ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race/ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03‐1.47 [P = .02]), whereas Asian/Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57‐0.77 [P < .001]).CONCLUSIONSDespite having localized disease that met transplantation criteria, nearly 50% of the large nationwide cohort of patients with HCC in the current study received only supportive care and had dismal 5‐year relative survival rates, especially among black patients. Cancer 2014;120:1725–1732. © 2014 American Cancer Society.

Primary IGH translocations involving seven recurrent partner loci and oncogenes are present in about 40% of multiple myeloma tumors. Secondary IGH rearrangements, which occur in a smaller fraction of tumors, usually are complex structures, including insertions or translocations that can involve three chromosomes, and often with involvement of MYC. The main approach to detect IGH rearrangements is interphase—but sometimes metaphase—FISH strategies that use a telomeric variable region probe and a centromeric constant region/ Eα enhancer or 3′ flanking probe to detect a separation of these two probes, or a fusion of these probes with probes located at nonrandom partner sites in the genome. We analyzed 18 myeloma cell lines for detection discrepancies among Vysis, Cytocell, and in‐house IGH probe sets that hybridize with differing sequences in the IGH locus. There were no detection discrepancies for the three telomeric IGH probes, or for unrearranged IGH loci or primary IGH translocations using the centromeric IGH probes. However, the majority of complex IGH rearrangements had detection discrepancies among the three centromeric IGH probes. © 2014 Wiley Periodicals, Inc.