The genome-wide landscape of C:G > T:A polymorphism at the CpG contexts in the human population.

Background: The C:G > T:A substitution at the CpG dinucleotide contexts is the most frequent substitution type in genome evolution. The mutational process is obviously ongoing in the human germline; however, its impact on common and rare genomic polymorphisms has not been comprehensively investigated yet. Here we observed the landscape and dynamics of C:G > T:A substitutions from population-scale human genome sequencing datasets including ~ 4300 whole-genomes from the 1000 Genomes and the pan-cancer analysis of whole genomes (PCAWG) Project and ~ 60,000 whole-exomes from the Exome Aggregation Consortium (ExAC) database.

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study.

Background: NUT carcinoma is a rare aggressive disease caused by fusion, and upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC-targeting agents against patient-derived NUT carcinoma cell lines.

Materials And Methods: Thirteen patients with NUT carcinoma were evaluated for p53, C-MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD-L1) by immunohistochemistry.

Human glioblastoma arises from subventricular zone cells with low-level driver mutations.

Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates.

Mutalisk: a web-based somatic MUTation AnaLyIS toolKit for genomic, transcriptional and epigenomic signatures.

Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome.

Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas.

Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs.

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

Background: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue.

Results: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.

Mechanisms and Consequences of Cancer Genome Instability: Lessons from Genome Sequencing Studies.

During tumor evolution, cancer cells can accumulate numerous genetic alterations, ranging from single nucleotide mutations to whole-chromosomal changes. Although a great deal of progress has been made in the past decades in characterizing genomic alterations, recent cancer genome sequencing studies have provided a wealth of information on the detailed molecular profiles of such alterations in various types of cancers. Here, we review our current understanding of the mechanisms and consequences of cancer genome instability, focusing on the findings uncovered through analysis of exome and whole-genome sequencing data.

Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation.

The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored.

Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking.

Primary cilia exert a profound impact on cell signalling and cell cycle progression. Recently, actin cytoskeleton destabilization has been recognized as a dominant inducer of ciliogenesis, but the exact mechanisms regulating ciliogenesis remain poorly understood. Here we show that the actin cytoskeleton remodelling controls ciliogenesis by regulating transcriptional coactivator YAP/TAZ as well as ciliary vesicle trafficking.

The Impact of Molecularly Targeted Treatment on Direct Medical Costs in Patients with Advanced Non-small Cell Lung Cancer.

Purpose: To investigate the impact of targeted treatment on direct medical costs of patients with advanced non-small cell lung cancer (NSCLC).

Materials And Methods: Medical records of 108 stage IIIB/IV NSCLC patients treated in Seoul National University Hospital between 2003 and 2009, were reviewed to collect medical resources utilization data from the diagnosis of stage IIIB/IV NSCLC to the end of active anti-cancer treatment. The direct medical costs were calculated by multiplying the number of medical resources used by the unit price.

Prediction of survival in terminally ill cancer patients at the time of terminal cancer diagnosis.

Purpose: We aimed to investigate the prognostic factors that can predict terminal stage survival (TSS) at the time of terminal cancer diagnosis.

Methods: We prospectively evaluated 141 patients immediately after the diagnosis of terminal cancer by their attending oncologists. A total of 32 factors, including performance status, clinical prediction of survival, time to terminal cancer (TTC), clinical symptoms, signs, and laboratory tests including the neutrophil-lymphocyte ratio (NLR), were analyzed.

Terminal cancer patients' and their primary caregivers' attitudes toward hospice/palliative care and their effects on actual utilization: A prospective cohort study.

Background: Previous studies on hospice/palliative care indicated that patients' socio-demographic factors, disease status, and availability of health-care resources were associated with hospice/palliative care utilization. However, the impact of family caregivers on hospice/palliative care utilization has not been thoroughly investigated.

Aim: To evaluate the association between attitudes toward hospice/palliative care of both patients with terminal cancer (defined as progressive, advanced cancer in which the patient will die within months) and their family caregivers and utilization of inpatient hospice/palliative care facilities.

Epidermal growth factor receptor tyrosine kinase inhibitors vs conventional chemotherapy in non-small cell lung cancer harboring wild-type epidermal growth factor receptor: a meta-analysis.

Importance: Current guidelines recommend both epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type (WT) EGFR who were previously treated for non-small cell lung cancer (NSCLC). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR.

Objective: To determine the association between first-generation EGFR TKI vs chemotherapy and survival in advanced NSCLC patients with WT EGFR.

The Understanding of Terminal Cancer and Its Relationship with Attitudes toward End-of-Life Care Issues.

Background: Although terminal cancer is a widely used term, its meaning varies, which may lead to different attitudes toward end-of-life issues. The study was conducted to investigate differences in the understanding of terminal cancer and determine the relationship between this understanding and attitudes toward end-of-life issues.

Methods: A questionnaire survey was performed between 2008 and 2009.

Efficacy of exemestane in korean patients with metastatic breast cancer after failure of nonsteroidal aromatase inhibitors.

Purpose: Exemestane has shown good efficacy and tolerability in postmenopausal women with hormone receptor-positive metastatic breast cancer. However, clinical outcomes in Korean patients have not yet been reported.

Methods: Data on 112 postmenopausal women with metastatic breast cancer were obtained retrospectively.

Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT.

Introduction: ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation.

Methods: Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively.

The transcriptional landscape and mutational profile of lung adenocarcinoma.

All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers.

Surrogate decision-making in Korean patients with advanced cancer: a longitudinal study.

Purpose: Although surrogate decision-making in cancer patients is well-known, few studies investigating the prevalence of surrogate decision-making over time have been reported. The objectives of this study were to investigate the level of surrogate decision-making in advanced cancer patients over time and the impact of demographic and clinical variables on surrogate decision-making.

Methods: The level of surrogate decision-making was measured in 572 consecutive cancer patients who died between January 1 and December 31, 2009.

Differential sensitivities to tyrosine kinase inhibitors in NSCLC harboring EGFR mutation and ALK translocation.

Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer (NSCLC) are mutually exclusive. However, several exceptional cases harboring both genetic alterations have been reported. In this study, a total of 444 patients with lung adenocarcinoma were examined for their EGFR and ALK status at Seoul National University Hospital between July 2008 and September 2011.

Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement in advanced non-small cell lung cancer patients.

Fluorescence in situ hybridization (FISH) is currently used to detect non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene rearrangement, who are candidates for ALK inhibitor therapy. However, FISH may not be a practical method for screening for ALK-positive patients in a large population due to its cost and difficulty in interpretation. We investigated the role of immunohistochemistry (IHC) to screen for ALK rearrangement in advanced NSCLC.

Comparative analyses of overall survival in patients with anaplastic lymphoma kinase-positive and matched wild-type advanced nonsmall cell lung cancer.

Background: The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) who were managed in the pre-ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild-type (WT) patients.

Methods: Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy.

Acute lymphoblastic leukemia in elderly patients: a single institution's experience.

Background/aims: We investigated the clinical characteristics and prognosis of elderly patients with acute lymphoblastic leukemia (ALL).

Methods: We reviewed the clinical data, laboratory findings, bone marrow findings, and cytogenetic analysis of elderly patients (≥ 60 years) with ALL, and data of an additional 101 younger adult patients (< 60 years) with ALL were reviewed for comparison.

Results: Twenty-six elderly patients (≥ 60 years) and 101 younger adult patients (< 60 years) with ALL were retrospectively enrolled.