Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer.

A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis.

Gene expression and risk of leukemic transformation in myelodysplasia.

Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic disorders with a highly variable prognosis. To identify a gene expression-based classification of myelodysplasia with biological and clinical relevance, we performed a comprehensive transcriptomic analysis of myeloid neoplasms with dysplasia using transcriptome sequencing. Unsupervised clustering of gene expression data of bone marrow CD34 cells from 100 patients identified 2 subgroups.

Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively.

Large-scale DNA Barcode Library Generation for Biomolecule Identification in High-throughput Screens.

High-throughput screens allow for the identification of specific biomolecules with characteristics of interest. In barcoded screens, DNA barcodes are linked to target biomolecules in a manner allowing for the target molecules making up a library to be identified by sequencing the DNA barcodes using Next Generation Sequencing. To be useful in experimental settings, the DNA barcodes in a library must satisfy certain constraints related to GC content, homopolymer length, Hamming distance, and blacklisted subsequences.

Loss of DNA Damage Response in Neuroblastoma and Utility of a PARP Inhibitor.

Background: Neuroblastoma (NB) is the most common solid tumor found in children, and deletions within the 11q region are observed in 11% to 48% of these tumors. Notably, such tumors are associated with poor prognosis; however, little is known regarding the molecular targets located in 11q.

Methods: Genomic alterations of ATM , DNA damage response (DDR)-associated genes located in 11q ( MRE11A, H2AFX , and CHEK1 ), and BRCA1, BARD1, CHEK2, MDM2 , and TP53 were investigated in 45 NB-derived cell lines and 237 fresh tumor samples.

Adaptive NetworkProfiler for Identifying Cancer Characteristic-Specific Gene Regulatory Networks.

There is currently much discussion about sample (patient)-specific gene regulatory network identification, since the efficiently constructed sample-specific gene networks lead to effective personalized cancer therapy. Although statistical approaches have been proposed for inferring gene regulatory networks, the methods cannot reveal sample-specific characteristics because the existing methods, such as an L-type regularization, provide averaged results for all samples. Thus, we cannot reveal sample-specific characteristics in transcriptional regulatory networks.

Prognostic relevance of genetic alterations in diffuse lower-grade gliomas.

Background: Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown.

Methods: Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308).

Requirement of glycosylation machinery in TLR responses revealed by CRISPR/Cas9 screening.

The Toll family of receptors sense microbial products and activate a defense response. The molecular machinery required for the TLR response is not yet fully understood. In the present study, we used a clustered, regularly interspaced, short palindromic repeats (CRISPR)/CAS9 screening system to study TLR responses.

Improvement in the rate of inadequate pharmaceutical treatment by orthopaedic surgeons for the prevention of a second fracture over the last 10 years.

Background: We have previously reported that the low rate of osteoporosis patients treated with anti-osteoporotic drugs following surgical treatment for the first fragility fractures by orthopaedic surgeons during 3 years from 2000 to 2003 was only 13.1%. Ten years have now passed our previous study, and we hypothesized that the rate of appropriate pharmacologic treatment for the prevention of secondary fractures has improved.

Genetic heterogeneity of uncharacterized childhood autoimmune diseases with lymphoproliferation.

Autoimmune diseases in children are rare and can be difficult to diagnose.  Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes.

Identification of a p53-repressed gene module in breast cancer cells.

The p53 protein is a sophisticated transcription factor that regulates dozens of target genes simultaneously in accordance with the cellular circumstances. Although considerable efforts have been made to elucidate the functions of p53-induced genes, a holistic understanding of the orchestrated signaling network repressed by p53 remains elusive. Here, we performed a systematic analysis to identify simultaneously regulated p53-repressed genes in breast cancer cells.

Identification of a p53 target, CD137L, that mediates growth suppression and immune response of osteosarcoma cells.

p53 encodes a transcription factor that transactivates downstream target genes involved in tumour suppression. Although osteosarcoma frequently has p53 mutations, the role of p53 in osteosarcomagenesis is not fully understood. To explore p53-target genes comprehensively in calvarial bone and find out novel druggable p53 target genes for osteosarcoma, we performed RNA sequencing using the calvarial bone and 23 other tissues from p53 and p53 mice after radiation exposure.

Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14.

Genome-wide association studies are a powerful tool for searching for disease susceptibility loci. Several studies identifying single nucleotide polymorphisms (SNP) connected intimately to the onset of colorectal cancer (CRC) have been published, but there are few reports of genome-wide association studies in Japan. To identify genetic variants that modify the risk of CRC oncogenesis, especially in the Japanese population, we performed a multi-stage genome-wide association study using a large number of samples: 1846 CRC cases and 2675 controls.

Molecular studies reveal and gene fusions displaced in a case of infantile acute lymphoblastic leukemia with complex karyotype.

The present report describes a unique infantile acute lymphoblastic leukemia (ALL) case with cryptic mixed-lineage leukemia (MLL) rearrangements with 11q23 chromosomal translocation. break-apart signals were identified by fluorescence hybridization, and transcriptome sequencing revealed -myeloid/lymphoid or mixed-lineage leukemia; translocated To, 10 ()/ fusion transcripts. Analysis also revealed a previously unreported /-homeobox protein Mohawk () transcript, where the 5' portion of at 10p12.

Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia.

The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.

Identification of an immunogenic neo-epitope encoded by mouse sarcoma using CXCR3 ligand mRNAs as sensors.

The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3 immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems.

The Transcriptional Landscape of p53 Signalling Pathway.

Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53 or p53 mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53 mice, while 2576 genes were downregulated.

Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia.

Maffucci syndrome is a nonhereditary disorder caused by somatic mosaic isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations and is characterized by multiple enchondromas along with hemangiomas. Malignant transformation of enchondromas to chondrosarcomas and secondary neoplasms, such as brain tumors or acute myeloid leukemia, are serious complications. A 15-year-old female with Maffucci syndrome developed B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Correction: Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

[This corrects the article DOI: 10.1371/journal.pgen.

Common Variable Immunodeficiency Caused by FANC Mutations.

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients.

Genome-wide screening of DNA methylation associated with lymph node metastasis in esophageal squamous cell carcinoma.

Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC.