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

Lemierre syndrome is characterized by anaerobic bacterial infection in the head and neck and clinical or radiological evidence of internal jugular vein thrombophlebitis. The most common pathogens are Fusobacterium species, particularly Fusobacterium necrophorum. Septic emboli resulting from infected thrombophlebitis of the internal jugular vein leads to metastatic infections involving lung, liver, kidney, bone and central nervous system. The accurate diagnosis and treatment is important because it may be associated with a high mortality rate if untreated. We present a case of 28-year-old man with an atypical history for the diagnosis of Lemierre syndrome, which showed no definite evidence of internal jugular thrombophlebitis.
Adult ; Bacterial Infections ; Central Nervous System ; Diagnosis ; Empyema ; Fusobacterium ; Fusobacterium necrophorum ; Head ; Humans ; Jugular Veins ; Kidney ; Lemierre Syndrome* ; Liver ; Lung ; Mortality ; Neck ; Thrombophlebitis

OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.
Anxiety ; Brain-Derived Neurotrophic Factor ; Depression ; Genotype ; Health Surveys ; Humans ; Linear Models ; Polymorphism, Genetic ; Quality of Life* ; Receptor, Serotonin, 5-HT1A* ; Receptors, Glucocorticoid ; Renal Dialysis* ; Serotonin*

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia, splenomegaly, and hypercellular bone marrow without Philadelphia chromosome. Diagnosis of CNL requires exclusion of identifiable causes of reactive neutrophilia, such as infection and tumors. Our patient presented with general weakness and weight loss. Computed tomography (CT) showed a mass in the distal rectum, which was confirmed to be an adenocarcinoma by colonoscopic biopsy. Positron emission tomography-CT showed multiple liver, bone, and lymph node metastases. Liver and lymph node biopsies revealed neutrophilic infiltration with no evidence of adenocarcinoma. The pathological findings of the bone marrow were compatible with CNL. Cytogenetic analysis revealed a normal karyotype, and molecular analysis was negative for BCR/ABL. Here, we present a 73 year-old man diagnosed with concurrent CNL and rectal cancer.
Adenocarcinoma ; Biopsy ; Bone Marrow ; Cytogenetic Analysis ; Diagnosis ; Electrons ; Humans ; Karyotype ; Leukemia ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction ; Leukocytosis ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Neutrophils ; Philadelphia Chromosome ; Rectal Neoplasms* ; Rectum ; Splenomegaly ; Weight Loss

The incidence of thyroid cancer has increased rapidly worldwide, although most patients can survive for a long time without developing symptoms. While most thyroid cancers are treated with thyroidectomy alone, some patients are given additional radioactive iodine (RAI) in the form of 131I to treat thyroid cancer metastasis. RAI is associated with acute and chronic complications. Secondary malignancies are the most important in long-term cancer survivors. While many studies have reported the occurrence of acute myeloid leukemia after high-dose RAI, there are few reports on chronic myeloid leukemia (CML) after low-dose RAI treatment. Moreover, previous cases of CML following thyroid cancer were reported before the tyrosine kinase inhibitor (TKI) era. Here, we describe two cases of CML following thyroid cancer that were successfully treated with second-generation TKIs.
Humans ; Incidence ; Iodine* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Leukemia, Myeloid, Acute ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Survivors ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

We report two cases of endoscopic submucosal dissection (ESD) for recurrent or residual esophageal squamous cell carcinoma (ESCC) lesions after chemoradiotherapy for advanced esophageal cancer. Case 1 involved a 64-year-old man who had previously undergone chemoradiotherapy for advanced ESCC and achieved a complete response (CR) for 22 months, until metachronous recurrent superficial ESCC was detected on follow-up esophagogastroduodenoscopy (EGD). We performed ESD and found no evidence of recurrence for 24 months. Case 2 involved a 59-year-old man who had previously undergone chemoradiotherapy for advanced ESCC. He responded favorably to treatment, and most of the tumor had disappeared on follow-up EGD 4 months later. However, there were two residual superficial esophageal lugol-voiding lesions. We performed ESD, and he had a CR for 32 months thereafter. ESD can be considered a viable treatment option for recurrent or residual superficial ESCC after chemoradiotherapy for advanced esophageal cancer.
Carcinoma, Squamous Cell ; Chemoradiotherapy* ; Endoscopy, Digestive System ; Esophageal Neoplasms* ; Follow-Up Studies ; Humans ; Middle Aged ; Recurrence

A 56-year-old woman with emphysematous pyelonephritis underwent an emergent left nephrectomy due to her religious creed. Postoperative hemoglobin level was decreased to 4.4 g/dL from preoperative value of 13.9 g/dL. The patient completely recovered without transfusion and was discharged on the 40th postoperative day without complication.
Anemia* ; Female ; Humans ; Middle Aged ; Nephrectomy* ; Pyelonephritis

Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (P < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, P = 0.027). OR and P value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed P value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.
Adenocarcinoma/*genetics/pathology ; Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Cell Adhesion Molecules, Neuronal/*genetics ; Chromosomes, Human, Pair 2 ; Female ; *Genome-Wide Association Study ; Genotype ; Humans ; Logistic Models ; Lung Neoplasms/*genetics/pathology ; Models, Genetic ; Nerve Tissue Proteins/*genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Republic of Korea

PURPOSE: c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer. MATERIALS AND METHODS: The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry. RESULTS: SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein. CONCLUSION: Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity to SU11274 in lung cancer.
Apoptosis ; Blotting, Western ; Caspase 3 ; Down-Regulation ; Flow Cytometry ; Growth Inhibitors ; Humans ; Indoles ; Lung ; Lung Neoplasms ; Molecular Targeted Therapy ; Piperazines ; Protein-Tyrosine Kinases ; Puma ; Sulfonamides ; Transplantation, Heterologous ; Tumor Burden ; Tumor Suppressor Protein p53 ; Up-Regulation

PURPOSE: The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population. MATERIALS AND METHODS: A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk. RESULTS: Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer. CONCLUSION: JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.
Haplotypes ; Humans ; Janus Kinase 3 ; Janus Kinases ; Korea ; Logistic Models ; Lung ; Lung Neoplasms ; Promoter Regions, Genetic ; Protein-Tyrosine Kinases