PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

Surgery for pathologic hip fracture poses significant challenges regarding the fixation of fracture and management of the original tumor lesion. An extensive destruction of the femoral neck and intertrochanteric region by benign or malignant lesions complicated by a pathological fracture generally necessitates total hip arthroplasty; however, in adolescents and young adults, preservation of the hip is preferable. We present a 14-year-old female patient, who sustained a pathological intertrochanteric fracture through a pre-existing aneurysmal bone cyst. Several operative interventions with internal fixation and bone graft were unsuccessful, and combined nonunion and progression of osteolysis around the compression hip screw eventually caused femoral head collapse, mimicking osteonecrosis. Hip preservation and resolution of the original tumor were achieved by free vascularized fibular graft.
Adolescent ; Aneurysm ; Arthroplasty, Replacement, Hip ; Bone Cysts ; Female ; Femur Neck ; Fractures, Spontaneous ; Head* ; Hip ; Humans ; Osteolysis ; Osteonecrosis ; Transplants* ; Young Adult

Shoulder dislocation is the most common dislocation presenting to the emergency department. In old age, the attempt of closed reduction is made with caution in order to prevent iatrogenic fracture around the shoulder. We report two cases of iatrogenic fractures of humeral shaft and anatomical neck in female patients older than 70 years old, which occurred during the manual closed reduction. One patient was proved as first-time and the other was recurrent. In addition, the second case had a massive irreparable rotator cuff tear. Those patients were treated successfully with humeral nailing and reverse total shoulder arthroplasty, respectively.
Arthroplasty ; Dislocations ; Emergency Service, Hospital ; Female ; Fracture Fixation, Intramedullary ; Humans ; Humeral Fractures* ; Neck ; Rotator Cuff ; Shoulder Dislocation* ; Shoulder* ; Tears

PURPOSE: We aimed to report the clinical results of diaphyseal osteoplasty and primary soft tissue closure in recalcitrant poor skin lesion with superficial or localized bone infection on the anterior shin after chronic osteomyelitis. MATERIALS AND METHODS: We retrospectively reviewed 7 patients with poor shin skin lesion complicated by superficial and localized bone infection after chronic osteomyelitis. The average duration of chronic osteomyelitis was 39 years. After excision of the poor skin lesion, diaphyseal osteoplasty of the tibia was performed for the resection of infected bone and primary closure of the soft tissue defect. Postoperative results were evaluated with recovery of skin lesion, the amount of bone resection by osteoplasty and complications including recurrence of osteomyelitis. RESULTS: Mean size of excised skin lesion during surgery was 3.0×14.1 cm and successful primary closures of the defect were possible in all cases. All shin skin lesions were recovered and the amount of resected bone was mean of 18.7% of the anteroposterior diameter of the tibia. There was no recurrence of skin lesion, osteomyelitis or stress fracture. CONCLUSION: After treatment of a previous intramedullary infection in chronic osteomyelitis of the tibia, recalcitrant poor shin skin lesion complicated with superficial or localized bone infection was effectively recovered by diaphyseal osteoplasty and primary soft tissue closure. This procedure is relatively simple compared to other surgeries and effective in recovery of healthy shin skin without recurrence of osteomyelitis.
Fractures, Stress ; Humans ; Osteomyelitis* ; Recurrence ; Retrospective Studies ; Skin* ; Tibia*

Anaphylactic transfusion reaction is caused by deficiency of certain protein(s) in the recipient. We report on the experience of platelet count recovery using washed platelets for transfusion in a patient who developed an anaphylactic transfusion reaction. A 50-year old male diagnosed with angioimmunoblastic T-cell lymphoma was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Immediately after starting transfusion of apheresis platelets, he began sweating and complained of visual impairment, chest discomfort, and abdominal pain. Both systolic and diastolic blood pressures and oxygen saturation monitored by pulse oximetry were decreased. Platelet transfusion was discontinued immediately and hydrocortisone was administered, and the symptoms and signs were resolved within two hours. Laboratory test using post-transfusion blood showed no apparent evidence of hemolysis. Platelet washing procedure using normal saline three times was newly set to prevent anaphylactic reaction in the patient. Transfusions of washed platelets were performed 20 times for 60 days, and the patient showed no anaphylactic reaction during this period. He showed no evidence of immunoglobulin A, haptoglobin, C3, or C4 deficiencies. We confirmed that washed platelet transfusion is highly effective for prevention of anaphylactic transfusion reaction.
Abdominal Pain ; Anaphylaxis ; Blood Component Removal ; Blood Group Incompatibility* ; Blood Platelets* ; Drug Therapy ; Haptoglobins ; Hematopoietic Stem Cell Transplantation ; Hemolysis ; Humans ; Hydrocortisone ; Immunoglobulin A ; Lymphoma, T-Cell ; Male ; Oximetry ; Oxygen ; Platelet Count ; Platelet Transfusion* ; Sweat ; Sweating ; Thorax ; Vision Disorders

The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second (FEV1) by aspirin provocation, two variations (rs7664091 and rs12500534) and one haplotype (TEC_BL2_ht4) showed nominal associations with FEV1 decline (p = 0.03-0.04). However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.
Aspirin ; Asthma ; Calcium ; Forced Expiratory Volume ; Gene Expression ; Haplotypes ; Logistic Models ; Mast Cells ; Phosphotransferases ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Tyrosine

BACKGROUND: The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1alpha is homologous with murine Reg1, we investigated whether common variants in Reg1alpha are associated with type 2 diabetes in the Korean population. METHODS: We sequenced the Reg1alpha gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects. RESULTS: No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009). CONCLUSION: Polymorphisms in the Reg1alpha were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.
Animals ; Diabetes Mellitus, Type 2 ; DNA ; Haplotypes ; Humans ; Mice

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (beta1) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and P(corr)=0.05). The minor allele frequency (MAF) of ITGB1 haplotype-2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.
Carcinoma, Hepatocellular ; Gene Frequency ; Haplotypes ; Humans ; Integrins ; Linkage Disequilibrium ; Liver ; Logistic Models ; Neoplasm Metastasis ; Proportional Hazards Models ; Proteins ; Sequence Analysis, DNA

Serpin peptidase inhibitor, Clade B (ovalbumin), Member 5 (SERPINB5), also known as maspin, is a potent tumor suppressor gene. It has correlations with many tumor cells, from pancreas cancer to breast cancer, so it is possible that it may also affect liver cancer. There has also been a report that SERPINB12, a gene placed right next to SERPINB5, is expressed in liver. For this study, 32 polymorphisms were identified in SERPINB5 by direct DNA sequencing, and 11 of them were selected to be tested with a larger scale subjects. The association of the 11 SERPINB5 polymorphisms with Hepatitis B virus (HBV) clearance, hepatocellular carcinoma (HCC) occurrence and the onset age of HCC were analyzed. There were no significant associations found between 11 SERPINB5 polymorphisms and HBV clearance. In the case of HCC occurrence, one of the haplotypes (ht) showed association with HCC occurrence (OR=2.26, p=0.005, P(Cor)=0.05), albeit with a low statistical power (40.8%) and haplotype frequency (0.052). Further study with a bigger sample size will be needed to clearly verify the association between ht5 and HCC occurrence.
Age of Onset ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Genes, Tumor Suppressor ; Genes, vif ; Haplotypes ; Hepatitis B virus ; Liver ; Liver Neoplasms ; Pancreatic Neoplasms ; Sample Size ; Sequence Analysis, DNA ; Serpins

OBJECTIVE: The risk of macrosomia in diabetic complicated pregnancy is increased perinatal morbidity. But it is difficult to predict adverse outcomes after birth with conventional diagnostic tools of diabetes in pregnant women. We evaluated the birth-weight between diabetic and non-diabetic pregnant women based on gestational weeks to determine adverse pregnancy outcome. METHODS: We selected 166 diabetic complicated pregnant women delivered between January 2005 and December 2008 and 248 non-diabetic pregnant women at same period. We compared the birth-weight between two groups in relation to the gestational age below and over 37 weeks. Fetal anomalies, fetal death, and multifetal pregnancy were excluded in this study. And we also evaluated the incidence of baby who had birth-weight 3.8 kg or more and their neonatal outcomes between two groups. RESULTS: There were 4.9% (166/3404) of diabetic complicated pregnancies. The preterm births (birth before 37 weeks of gestation) were occurred 32.5% (54/166) and term births (birth after 37 weeks of gestation) were 67.5% (112/166). The mean birth-weight in preterm birth showed 2,492 g of gestational diabetes, 3,315 g of pregestational diabetes and 2,118 g of control group (P=0.001). The mean birth-weight and gestational age at delivery in term birth showed pregestational diabetes and gestational diabetes were heavier and shorter than those of control group (P=0.002). The incidence of 3.8 kg or more of birth-weighted baby appeared 43.5% (10/23) of pregestional diabetes, 16.8% (24/143) of gestational diabetes and 8.5% (21/248) of control group (P=0.000). The Apgar score less than 7 at minutes of neonate were more frequent in pregestational and gestational diabetes than that of control group (P=0.013). CONCLUSION: It is important to classify the type of diabetes during pregnancy and there should be needed to predict adverse pregnancy outcomes including macrosomia.
Apgar Score ; Diabetes, Gestational ; Female ; Fetal Death ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Parturition ; Pregnancy ; Pregnancy Outcome ; Pregnant Women ; Premature Birth ; Term Birth