Identification of the novel HLA-C*03 allele, HLA-C*03:03:35.

The new allele HLA-C*03:03:35 showed one nucleotide difference with C*03:03:01:01 at position 408 (G>T).

A new HLA-DQB1*04 allele, HLA-DQB1*04:01:05, identified in a Korean individual.

HLA-DQB1*04:01:05 differs from DQB1*04:01:01 by a single nucleotide substitution at codon 30 (TAC>TAT).

SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination and turnover of c-MYC oncoprotein.

The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN). We found that SPOPWT can physically interact with c-MYC protein and, upon exogenous expression in vitro, can promote c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by introducing PC-associated SPOP mutants or upon knockdown of SPOP via short-hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in transcriptomic signatures associated with SPOPMT. Likewise, we observed strong inverse correlation between c-MYC activity and SPOP mRNA levels in two independent PC patient cohorts. The core SPOPMT;MYCHigh transcriptomic response, defined by the overlap between the SPOPMT and c-MYC transcriptomic programmes, was also associated with inferior clinical outcome in human PCs. Finally, the organoid-forming capacity of Spop-null murine prostate cells was more sensitive to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC upregulation functionally contributes to the proliferative phenotype of Spop knock-out prostates. Taken together, our data highlight SPOP as an important regulator of luminal epithelial cell proliferation and c-MYC expression in prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help explain the frequent inactivation of SPOP in human PC. We propose SPOPMT-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus.

Identification of a novel HLA-B*40 allele, HLA-B*40:332, in a Korean individual.

HLA-B*40:332 differs from B*40:01:02 by 1 nucleotide difference at nucleotide position 439.

Identification of a novel allele, HLA-A*26:01:01:03N, by full-length genome sequencing.

The HLA-A*26:01:01:03N allele shows a single nucleotide difference compared with HLA-A*26:01:01:01 in intron 4(1846 G>A).

Identification of a novel HLA-A*29 allele, HLA-A*29:01:09, by sequence-based typing in a Korean individual.

HLA-A*29:01:09 differs from A*29:01:01:01 by one nucleotide difference at nucleotide position 414.

Identification of a novel HLA-C*03 variant allele, C*03:280 by sequence-based typing.

The new allele, HLA-C*03:280 differs from C*03:04:01 by one nucleotide substitution at codon 35 (CGG→CAG).

Sequence variations of the locus-specific 5' untranslated regions of SLA class I genes and the development of a comprehensive genomic DNA-based high-resolution typing method for SLA-2.

The genetic diversity of the major histocompatibility complex (MHC) class I molecules of pigs has not been well characterized. Therefore, the influence of MHC genetic diversity on the immune-related traits of pigs, including disease resistance and other MHC-dependent traits, is not well understood. Here, we attempted to develop an efficient method for systemic analysis of the polymorphisms in the epitope-binding region of swine leukocyte antigens (SLA) class I genes. We performed a comparative analysis of the last 92 bp of the 5' untranslated region (UTR) to the beginning of exon 4 of six SLA classical class I-related genes, SLA-1, -2, -3, -4, -5, and -9, from 36 different sequences. Based on this information, we developed a genomic polymerase chain reaction (PCR) and direct sequencing-based comprehensive typing method for SLA-2. We successfully typed SLA-2 from 400 pigs and 8 cell lines, consisting of 9 different pig breeds, and identified 49 SLA-2 alleles, including 31 previously reported alleles and 18 new alleles. We observed differences in the composition of SLA-2 alleles among different breeds. Our method can be used to study other SLA class I loci and to deepen our knowledge of MHC class I genes in pigs.

Identification of a novel HLA-B*40 variant allele, B*40:301, by sequence-based typing.

The new allele, HLA-B*40:301 differs from B*40:01:02 by one nucleotide substitution at codon 239 (AGA → AAA).

Identification of the novel allele, HLA-C*15:02:01:03, by full-length genomic sequencing.

The HLA-C*15:02:01:03 allele differs from the HLA-C*15:02:01:01 allele by a single-nucleotide substitution in the 5' untranslated region (-42 C>A).

A new HLA-B*15 allele, HLA-B*15:263, identified in a Korean individual.

HLA-B*15:263 differs from HLA-B*15:18:01 by a single nucleotide exchange at position 824, C>G (codon 251 TCT>TGT).

Identification of a new HLA-DRB1*04 allele, DRB1*04:10:03.

The new allele, DRB1*04:10:03, showed one nucleotide difference with DRB1*04:10:01 (705C>T).

A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer.

BACKGROUND: It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases. PATIENTS AND METHODS: We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome. RESULTS: The median age was 58 years (range, 29-85) with ECOG 0-1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2-20.0] in the SRS group and 15.3 months (95% CI, 7.2-23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy), P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance. CONCLUSIONS: Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients. CLINICAL TRIALS NUMBER: NCT01301560.

Identification of a novel HLA-A*02 allele, A*02:428, by sequence-based typing.

HLA-A*02:428 differs from A*02:06:01 by a non-synonymous mutation at codon 260 (CAT to GAT) in exon 4.

Density and types of calretinin-containing retinal ganglion cells in rabbit.

Single-cell injection with lipophilic dyes following immunocytochemistry is extremely valuable for revealing the morphology of a cell expressing a protein of interest, and is a more reliable technique for cell type classification than standard morphological techniques. This study focuses on calretinin (CR), which is used as a selective marker for distinct subpopulations of neurons in the rabbit retina. The present study used single-cell injection after immunocytochemistry to describe the density and types of CR-containing retinal ganglion cells (RGCs) in rabbit. The density of CR-immunoreactive cells in the rabbit RGC cell layer was 426cells/mm(2). CR-containing RGCs were identified by immunocytochemistry and were then iontophoretically injected with a lipophilic dye, DiI. Subsequently, confocal microscope was used to characterize the morphology of CR-immunoreactive RGCs based on their dendritic field size, branching pattern, and stratification of the inner plexiform layer. Our results show that 10 morphologically different types of rabbit RGCs expressed CR. CR-containing RGCs were heterogeneous in their morphology. This approach to integrate the selective expression of a particular protein with spatial patterns of dendritic arborization will lead to a better understanding of RGCs.

Initial report of the Korean Organ Transplant Registry: the first report of national kidney transplantation data.

PURPOSE: A national organ transplant registry is an indispensable organizational requirement for patient care, research, and planning. Even though the Korean Network for Organ Sharing (KONOS) has established a database for a waiting list, organ allocation, and incidence of organ transplantation since 2000, an integrated registry including post-transplantation data is needed for better understanding of organ transplantation. Recently, the Korean Society for Transplantation (KST) and the Korean Center for Disease Control (KCDC) designed a web-based organ transplant registry, named the Korean Organ Transplant Registry (KOTRY). As an initial project of KOTRY, we retrospectively analyzed kidney transplantations (KTs) performed in 2009 and 2010. METHODS: A total of 2292 KTs (91.9%) from 46 hospitals (80.7%) were collected and analyzed. Ninety-five elements related to KT were selected and analyzed. RESULTS: Proportions of male recipients and retransplantations were 58.4% and 7.1%, respectively. Even though glomerulonephritis was the most common cause of end-stage renal disease (ESRD) (28.4%), the number of diabetic nephropathy cases was increasing. The living donor (LD) to deceased donor (DD) ratio was 1.69:1. Because of a serious organ shortage in Korea, DD kidneys with a low initial estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m(2) (21.2%) and expanded criteria donors (ECDs; 18.3%) are frequently used. Other noticeable findings are the increasing number of wife donors and ABO-incompatible (ABOi) transplants for O(+) recipients. CONCLUSIONS: The epidemiological profile of transplantation is different from country to country. The number of organ transplantations in East Asian countries is rapidly growing, however, there are few epidemiological data about this region in the literature. With the establishment of KOTRY, it was possible to present the first nationwide epidemiological data of Korean KTs.

HLA-B*40:02:18, a new HLA-B*40 allele.

The new allele B*40:02:18 showed one nucleotide difference with B*40:02:01 at codon 111 (CGC/CGT).