Oncogenic signaling pathways and hallmarks of cancer in Korean patients with acral melanoma.

Acral melanoma (AM), a rare subtype of cutaneous melanoma, shows higher incidence in Asians, including Koreans, than in Caucasians. However, the genetic modification associated with AM in Koreans is not well known and has not been comprehensively investigated in terms of oncogenic signaling, and hallmarks of cancer. We performed whole-exome and RNA sequencing for Korean patients with AM and acquired the genetic alterations and gene expression profiles. KIT alterations (previously known to be recurrent alterations in AM) and CDK4/CCND1 copy number amplifications were identified in the patients. Genetic and transcriptomic alterations in patients with AM were functionally converge to the hallmarks of cancer and oncogenic pathways, including 'proliferative signal persistence', 'apoptotic resistance', and 'activation of invasion and metastasis', despite the heterogeneous somatic mutation profiles of Korean patients with AM. This study may provide a molecular understanding for therapeutic strategy for AM.

Comparison of 3 automated immunoassays for detection of anti-hepatitis A virus immunoglobulin M in a tertiary care hospital.

Three automated immunoassay kits for anti-Hepatitis A Virus (HAV) IgM-Architect, (Abbott Laboratories, USA), Elecsys (Roche Diagnostics, Germany), and ADVIA Centaur (Siemens Healthcare Diagnostics Inc., USA)-were compared. We included 178 consecutive samples, for which an anti-HAV IgM test was requested at Seoul National University Hospital from September 2009 to January 2010. Reviewing of medical records, reverse transcription (RT)-PCR for HAV RNA, or total anti-HAV assay were performed on 16 (9.0%) samples with discrepant results. The percent agreements (kappas) of the Architect and ADVIA Centaur, Architect and Elecsys, and ADVIA Centaur and Elecsys kits were 96.6% (0.91), 96.6% (0.92), and 97.8% (0.94), respectively. Eight out of 16 discrepant samples showed gray-zone values in Architect but were nonreactive in the others. Slightly earlier seroconversion was suspected in Elecsys. The 3 assays showed comparable performances with excellent agreements in a tertiary care hospital setting.

Clinical relevance of pretransplant HLA class II donor-specific antibodies in renal transplantation patients with negative T-cell cytotoxicity crossmatches.

BACKGROUND: We evaluated the clinical relevance of pretransplant donor-specific HLA antibodies (DSA) in renal transplantation patients who had negative T-cell cytotoxicity crossmatches. METHODS: From 328 consecutive renal transplant recipients, we selected 28 patients who had positive pretransplant (historical or at the time of transplantation) flow cytometry crossmatches, but negative T-cell cytotoxicity crossmatches at the time of transplantation. The presence of DSA and its level at the time of transplantation were retrospectively tested using Luminex single antigen assays. RESULTS: DSA was present in 16 (57.1%) of 28 patients. Biopsy-proven acute rejection (9 patients) occurred more frequently in patients with DSA than in those without DSA (56.3% vs. 0.0%; P=0.003). The positivity rate of class II DSA was significantly higher in patients with antibody-mediated rejection (AMR) than in those without AMR (100% vs. 21.7%; P=0.003). However, the positivity rate of class I DSA was not different between the two groups (40% vs. 40.9%). Among patients with class II DSA, those with AMR tended to have higher antibody levels (median fluorescence intensity, MFI) than those without AMR (16,359 vs. 5,910; P=0.056). A cut-off MFI value of 4,487 for class II DSA predicted the occurrence of AMR with good sensitivity and specificity (100% and 87.0%). CONCLUSIONS: In patients with negative T-cell cytotoxicity crossmatches, the presence of class II DSA and its level at the time of transplantation were associated with the occurrence of AMR. Pretransplant DSA measurement with Luminex single antigen assay would be useful in renal transplantation.

Establishment of a resource population of SLA haplotype-defined Korean native pigs.

The highly polymorphic porcine major histocompatibility complex (MHC), or the swine leukocyte antigens (SLA), has been repeatedly associated with variations in swine immune response to pathogens and vaccines as well as with production traits. The SLA antigens are also important targets for immunological recognition of foreign tissue grafts. We recently established a resource population of Korean native pigs as models for human transplantation and xenotransplantation research. In this study, 115 animals derived from three generations of the Korean native pigs were genotyped for three SLA class I (SLA-2, SLA-3 and SLA-1) and three SLA class II loci (DRB1, DQB1, DQA) using PCR with sequence-specific primers (PCR-SSP) at the allele group resolution. A total of seven SLA haplotypes (Lr-5.34, Lr-7.23, Lr-31.13, Lr-56.23, Lr-56.30, Lr-59.1, Lr-65.34), comprising six unique class I and five unique class II haplotypes, were characterized in the founding animals. Class I haplotype Lr-65.0 and class II haplotype Lr-0.34 were novel; and together with Lr-56.0 these haplotypes appeared to be breed-specific. In the progeny population, Lr-7.23 and Lr-56.30 appeared to be the most prevalent haplotypes with frequencies of 34.7% and 31.6%, respectively; the overall homozygosity was 27.4%. This resource population of SLA-defined Korean native pigs will be useful as large animal models for various transplantation and xenotransplantation experiments, as well as for dissecting the roles of SLA proteins in swine disease resistance and production traits.