A newly developed capture-based sequencing panel for genomic assay of lung cancer.

Background: The increase in genetic alterations targeted by specific chemotherapy in lung cancer has led to the need for universal use of more comprehensive genetic testing, which has highlighted the development of a lung cancer diagnostic panel using next-generation sequencing.

Objective: We developed a hybridization capture-based massively parallel sequencing assay named Friendly, Integrated, Research-based, Smart and Trustworthy (FIRST)-lung cancer panel (LCP), and evaluated its performance.

Methods: FIRST-LCP comprises 64 lung cancer-related genes to test for various kinds of genetic alterations including single nucleotide variations (SNVs), insertions and deletions (indels), copy number variations (CNVs), and structural variations.

HLA-corrected tumor mutation burden and homologous recombination deficiency for the prediction of response to PD-(L)1 blockade in advanced non-small-cell lung cancer patients.

Background: Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear.

Patients And Methods: We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy.

Immunosenescent characteristics of T cells in young patients following haploidentical haematopoietic stem cell transplantation from parental donors.

Objectives: Paediatric and adolescent patients in need of allogeneic haematopoietic stem cell transplantation (HSCT) generally receive stem cells from older, unrelated or parental donors when a sibling donor is not available. Despite encouraging clinical outcomes, it has been suggested that immune reconstitution accompanied by increased replicative stress and a large difference between donor and recipient age may worsen immunosenescence in paediatric recipients.

Methods: In this study, paired samples were collected at the same time from donors and recipients of haploidentical haematopoietic stem cell transplantation (HaploSCT).

Combination Therapy With Chemotherapy, Donor Lymphocyte Infusion With Concurrent Blinatumomab in Relapsed/Refractory Acute Precursor B-Lymphoblastic Leukemia.

The therapeutic approach for relapsed/refractory acute lymphoblastic leukemia (ALL) remains to be a challenge. The patient was diagnosed as B-cell ALL at 6 months of age and relapsed for the second time following repeat allogeneic hematopoietic stem cell transplantation (one after first complete remission [CR1] and the other after CR2). During blinatumomab monotherapy, he developed an extramedullary relapse.

Predominant Pathogenic Variants in Pediatric Follicular Thyroid Carcinomas.

Pediatric thyroid cancer has characteristics that are distinct from adulthood thyroid cancer. Due to its very low prevalence, little is known about the genetic characteristics of pediatric follicular thyroid cancer (FTC). We investigated genetic alterations in tumor tissues from 15 patients aged <20 years (median: 14.

Nitrosourea, etoposide and cyclophosphamide followed by autologous stem cell transplantation for pediatric lymphoma patients.

Treatment outcomes in pediatric lymphoma have improved substantially over the past 2 decades; however, the prognosis for patients with high risk or relapsed disease remains poor. We evaluated outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) in 56 pediatric lymphoma patients. Patients received nitrosourea (51 BCNU; 5 ACNU), etoposide, and cyclophosphamide (BEC; AEC).

Successful Treatment of a Korean Infant with Giant Cell Hepatitis with Autoimmune Hemolytic Anemia Using Rituximab.

Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine.

Clinical course of non-small cell lung cancer patients with dry pleural dissemination: Retrospective observational study.

We investigated the prognosis of patients with dry pleural dissemination (DPD) of non-small cell lung cancer (NSCLC) and the risk factors of developing to malignant pleural effusion (MPE).We retrospectively reviewed 104 patients with NSCLC and DPD, confirmed surgically from 1996 to 2016. Incidence rate and risk factors of MPE were analyzed statistically.

Effects of Actin Cytoskeleton Disruption on Electroporation In Vitro.

The role of actin fibers in cellular responses to external electric pulses is not clear yet. In this study, we utilized the blocker of actin polymerization, cytochalasin D (cytoD), and investigated its effects on the electropore generation. Eight 100 μs electric pulses of sub-kilovolt per centimeter voltage with 100 ms intervals were applied to adhered cells in vitro, and the membrane permeability was quantified using membrane-impermeable propidium iodide (PI) dye.

Erratum: Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia.

This corrects the article on e203 in vol. 34, PMID: 31373185.

Altered expression of fucosylation pathway genes is associated with poor prognosis and tumor metastasis in non‑small cell lung cancer.

Fucosylation is a post‑translational modification that attaches fucose residues to protein‑ or lipid‑bound oligosaccharides. Certain fucosylation pathway genes are aberrantly expressed in several types of cancer, including non‑small cell lung cancer (NSCLC), and this aberrant expression is associated with poor prognosis in patients with cancer. However, the molecular mechanism by which these fucosylation pathway genes promote tumor progression has not been well‑characterized.

Transcriptome-based molecular subtyping of non-small cell lung cancer may predict response to immune checkpoint inhibitors.

Objectives: We set out to investigate whether transcriptome-based molecular subtypes in lung adenocarcinoma and lung squamous cell carcinoma are predictive of the response to programmed cell death 1 blockade.

Methods: Molecular classification of non-small cell lung cancer was performed by unsupervised clustering of mRNA sequencing data from 87 lung adenocarcinoma and 101 lung squamous cell carcinoma specimens, and molecular subtypes were characterized according to their immunogenomic determinants. A prediction algorithm of molecular subtypes was applied to 35 patients with non-small cell lung cancer treated with programmed cell death 1 blockade to test its association with treatment response (GSE93157; the Barcelona cohort).

Clinical Application of Next-Generation Sequencing-Based Panel to Wild-Type Advanced Melanoma Identifies Key Oncogenic Alterations and Therapeutic Strategies.

Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid cancers to discover potential therapeutic targets. Here, we describe the results of a clinical NGS panel in patients with advanced melanoma. Thirty-six tumor tissues from patients with wild-type melanoma at Seoul National University Hospital (SNUH; Seoul, Republic of Korea) were collected and deep-sequenced using the SNUH FIRST-Cancer NGS panel to assess single-nucleotide variants, small insertions/deletions, copy number variations, and structural variations to estimate tumor mutation burden (TMB).

Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.

Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians.

Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent.

Cytomegalovirus disease in a retinoblastoma cohort: The role of preemptive screening.

Background: Cytomegalovirus (CMV) disease is underrecognized in children with retinoblastoma. This study investigated rates of CMV infection and disease in this specific population receiving chemotherapy.

Methods: From a cohort of 164 patients with retinoblastoma diagnosed from 2011 to 2018, 107 patients were evaluated for CMV infection determined by antigenemia assay or real-time PCR.

Successful preemptive therapy with single-dose rituximab for Epstein-Barr virus infection to prevent post-transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation.

Background: The efficacy of preemptive treatment containing rituximab to prevent post-transplant lymphoproliferative disease (PTLD) in children has not yet been fully elucidated.

Methods: We analyzed 19 pediatric patients who developed high Epstein-Barr virus (EBV) DNAemia (EBV viral load of greater than 40 000 copies/mL) after allogeneic hematopoietic stem cell transplantation (HSCT) and were preemptively administered rituximab. Rituximab was intravenously injected at a dose of 375 mg/m once the EBV viral load was greater than 40 000 copies/mL.

Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is rare in children and accounts for ≤15% of all myeloid leukemia cases. When we initiated this study with nilotinib, imatinib was the only tyrosine kinase inhibitor indicated for pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph+ CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph+ CML-CP.

Pharmacokinetics of high-dose carboplatin in children undergoing high-dose chemotherapy and autologous stem cell transplantation with BSA-based dosing.

Body surface area (BSA)-based carboplatin dosing is used in various centers due to practical issues of renal function-based dosing with area under the curve (AUC) measurement. Pharmacokinetic (PK) analysis of high-dose carboplatin was performed in pediatric solid tumor patients undergoing high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) with BSA-based dosing to calculate the AUCs achieved with this dosing method and to find the correlation between the PK and the renal functions and the adverse events. Carboplatin was administered as once daily intravenous doses at 300, 400, or 500 mg/m/day over 1 h for 3 or 4 days.

Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia.

Background: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV.

Methods: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed.

Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors.

Background: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors.

Methods: We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens.

Star Allele-Based Haplotyping versus Gene-Wise Variant Burden Scoring for Predicting 6-Mercaptopurine Intolerance in Pediatric Acute Lymphoblastic Leukemia Patients.

and are strong genetic determinants of thiopurine toxicity in pediatric acute lymphoblastic leukemia (ALL) patients. Since patients with or deficiency suffer severe adverse drug reactions, star (*) allele-based haplotypes have been used to predict an optimal 6-mercaptopurine (6-MP) dosing. However, star allele haplotyping suffers from insufficient, inconsistent, and even conflicting designations with uncertain and/or unknown functional alleles.

Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma.

Mutational processes giving rise to lung adenocarcinomas (LADCs) in non-smokers remain elusive. We analyzed 138 LADC whole genomes, including 83 cases with minimal contribution of smoking-associated mutational signature. Genomic rearrangements were not correlated with smoking-associated mutations and frequently served as driver events of smoking-signature-low LADCs.