5524 results for "*oma"

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• Genome and gene analysis of gastrointestinal cancer and elucidation of its clinicopathological significance

  Cancer develops through the accumulation of genetic and epigenetic aberrations. To identify sequential molecular alterations that occur during the development of hepatocellular carcinoma (HCC), we molecularly compared 52 early and 108 overt HCC samples by genome sequencing. Gene mutations in the p53/RB1 pathway, WNT pathway, MLLs, SWI/SNF complexes, and AKT/PI3K pathway were common in HCC. In the early phase of all entities, TERT was the most frequently upregulated gene owing to diverse mechanisms. Despite frequent somatic mutations in driver genes, including CTNNB1 and TP53, early HCC was a separate molecular entity from overt HCC as each had a distinct expression profile. Notably, WNT target genes were not activated in early HCC, regardless of CTNNB1 mutation status, because ?-catenin did not translocate into the nucleus due to the E-Cadherin/?-catenin complex at the membrane. Conversely, WNT targets were definitively upregulated in overt HCC with CTNNB1 mutation associated with downregulation of CDH1 and hypomethylation of CpG islands in the target genes. Similarly, cell cycle genes downstream of the p53/RB pathway were upregulated only in overt HCC with TP53 and/or RB1 gene mutations associated with chromosomal deletion of 4q and/or 16q. Differing from the expression profile, HCC was epigenetically distinguished into four subclasses: normal-like methylation, global-hypomethylation (favorable prognosis), stem-like methylation (poor prognosis), and CpG island methylation. These methylation statuses were globally maintained through HCC progression. Taken together, additional molecular events besides driver gene mutations cooperatively contribute to transcriptional activation of downstream targets as HCC progresses, according to the methylation status of the associated genes.

  Study JGAS000233

• Phylogenetic analysis of combined lobular and ductal carcinoma of the breast

  Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, we analyzed two combined lobular and ductal carcinoma (CLDC) cases, including one mixed ductal-lobular carcinoma (MDL) lesion, by next generation sequencing.

  Study JGAS000300

• Genomics characterization of primary central nervous system lymphoma

  Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to the central nervous system (CNS). Despite low tendency of systemic dissemination, its prognosis is poor with median overall survival of 2?4 years. Due to its rarity, knowledge of genomic alterations underling PCNSL pathogenesis is severely limited. Here we performed whole-exome sequencing on 44 PCNSL and paired normal specimens, revealing high penetrance of nonsynonymous somatic mutations in PIM1 (95.5%), BTG2 (88.6%) and MYD88 (81.8%). Interestingly we found oncogenic mutations in GRB2, and this effect was cancelled when transformed cells are treated with inhibitors to downstream kinases MAP2K1/2. Further, when tumor cells carries MYD88 mutations, the same mutations were also found at low frequency in peripheral blood mononuclear cells (PBMNC), implying that MYD88 mutation?positive precancerous cells originate outside CNS and develop to lymphoma with additional genetic hits that fit the CNS environment.

  Study JGAS000021

• Genome-wide copy number analysis of neuroblastoma

  Neuroblastoma is the most common extracranial solid tumor in childhood. Despite the improvement of risk-stratified therapies, overall survival rate of high-risk group is still as low as 40-50%. To investigate genome-wide copy number profiles of neuroblastoma, we performed SNP array analysis and PCR-based amplicon deep sequencing of neuroblastoma-related genes in 522 neuroblastoma samples.

  Study JGAS000046

• Identification of biomarkers for prediction of efficacy of microtubule inhibitors and antifolates in non-small cell lung cancer

  Identification of predictive markers based on transcriptome modules for microtubule inhibitors of lung adenocarcinoma patients

  Study JGAS000267

• Analysis of genomic alterations in dedifferentiated liposarcoma

  Multiomics analysis of rare cancers to identify genetic alterations related with pathogenesis and prognosis. To identification of genetics alterations of Dedifferentiated liposarcoma, DNAs and RNAs were extracted from dedifferentiated liposarcoma and paired non-cancer (normal) tissues. NGS libaraies were prepared by using Agilent SureSelect XT Human All Exon V5 + IncRNA kit for whole exome sequencing (WES) and TruSeq Stranded mRNA Prep kit or TruSeq RNA Access Library Prep kit (RNA seq). Sequencing was perfomred by Illumina HiSeq 2500.

  Study JGAS000182

• Amplicon sequencing of melanoma samples

  The types of biomarkers for skin tumors have been 1) biochemical markers in blood, urine, and body fluid, 2) histopathological markers, 3) genetic examination of tumor tissue, 4) tumor-susceptibility assessed by germ_x0002_line genetic examination. Biomarkers in a blood are frequently used in the treatment of cutaneous malignancies, but are not suitable for early detection of malignancies. Research on circulating tumor cells, cell free DNA, exosomes has been promoted in recent years, but clinical application is halfway. Based on these circumstances, the purpose of this study is to search for biomarkers for diagnosis, therapeutic effect, and follow-up of skin tumors, and to verify their usefulness.

  Study JGAS000351

• Comprehensive genomic analysis of patient derived orthotopic xenograft model in primary central nervous system lymphoma

  The purpose of this study is to investigate genetic background of orthotopic xenograft cells and aseess consistency with parent tumor cells. For exome sequencing, we used two distinct PCNSL cells (YML9 and YML11). We also performed RNA sequencing for 7 PCNSL patient tumor cells to compare NF-kB pathway activation.

  Study JGAS000178

• Epigenomic profiling of neuroendocrine lung cancer

  Heterogeneity of neuroendocrine (NE) differentiation in pulmonary high-grade NE carcinoma, mainly small-cell lung cancer (SCLC), has been recently explored based on the expression of lineage transcription factors such as ASCL1, NEUROD1 and POU2F3. However, molecular classification determined by these factors is not settled and accumulating evidence suggest that NE differentiation among lung cancers is more heterogeneous. Here, we investigated super-enhancer profiles of formalin-fixed paraffin-embedded tumor tissues from patients with a wide range of lung cancer with NE components, mainly large cell neuroendocrine carcinoma (LCNEC).

  Study JGAS000903

• Establishing stable brain tumor stem cell lines and translational research for new treatments

  Choroid plexus carcinomas (CPCs) have dismal prognoses with limited clinical options. A lack of characterized cell lines has hindered the development of new treatment strategies. Here, we perform whole genome sequencing analyses of two cell lines established from CPCs. Whole genome sequencing (WGS),was performed in CCHE-45 and NGT131 cell lines. Both cell lines harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis. Whole genome sequencing revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.

  Study JGAS000657

• Integrated Exome and RNA Sequencing of Dedifferentiated Liposarcoma

  Multiomics analysis of rare cancers to identify genetic alterations related with pathogenesis and prognosis. To identification of genetics alterations of Dedifferentiated liposarcoma, DNAs and RNAs were extracted from dedifferentiated liposarcoma and paired non-cancer (normal) tissues. NGS libaraies were prepared by using Agilent SureSelect XT Human All Exon V5 + IncRNA kit for whole exome sequencing (WES) and TruSeq Stranded mRNA Prep kit or TruSeq RNA Access Library Prep kit (RNA seq). Sequencing was perfomred by Illumina HiSeq 2500.

  Study JGAS000177

• Comprehensive gene expression analysis in renal cell carcinoma

  The goal is to elucidate the mechanisms of tumor initiation and progression, identify gene signatures associated with drug efficacy and adverse effects, and develop more accurate and reliable diagnostic methods and therapeutic targets.

  Study JGAS000913

• Epigenomic analysis of the human placenta and endometrium constituting the fetal-maternal interface

  This study aims to determine the reference epigenomes of the human placenta and endometrium, which constitute the fetal-meternal interface, for future use in studies of human diseases associated with reproduction and development. In the placenta, we focus on cytotrophoblast and syncytiotrophoblast cells (both at first trimester and at term) and, in the endometrium, we focus on epitherial cells (at the follicular and secretory phases) and stroma cells. These reference epigenomic data will be of valuable resource in studying disease-associated differences in epigenomic modification in the reproductive system. JGA submission accessions: JGA000117,JGA00000000117

  Study JGAS000107

• Integrated multi-omics analysis of pediatric hepatoblastoma

  Hepatoblastoma (HBL) is the most common malignant liver tumor in childhood and is clinically heterogeneous. In spite of its heterogeneity, the molecular basis responsible for the difference between low-risk and high-risk HBL has not been fully clarified. To address this issue, we carried out multi-omics analysis on 59 HBL samples to generate comprehensive profiles of gene mutation, copy-number alteration, DNA methylation and gene expression. By integrating these data, we aimed to unravel the heterogeneity of HBL and identify genetic determinants and therapy targets of high-risk HBL.

  Study JGAS000188

• Targeted exome sequencing identify compound heterozygous TYK2 mutations in patients with primary immunodeficiency who developed EBV-associated lymphoma

  In this study, we evaluated 2 siblings with primary immunodeficiency who developed EBV-associated lymphoma. Immunophenotyping of PBMCs revealed that both patients had significant T cell lymphopenia characterized by low na?ve CD4+ T cell counts. To identify the causative genetic mutations in the patients, we performed targeted exome sequencing using the Illumina MiSeq on the patients and their parents. The results showed a novel compound heterozygous mutations in the gene encoding tyrosine kinase 2 (TYK2) in the patients.

  Study JGAS000098

• intratumor heterogeneity in colorectal adenoma and carcinoma

  To investigate intratumor heterogeneity in precancerous lesions of colorectal cancers (PCRCs), we performed whole-exome sequencing of 53 tumor and 10 matched-normal samples from 10 laterally spreading tumors in the colon and rectum, which were histologically diagnosed as adenoma with/without adenocarcinoma.

  Study JGAS000092

• Genome-wide integrative analysis of pediatric pancreatoblastoma

  Pancreatoblastoma is the most common pancreatic malignancy of young children, but its molecular pathogenesis remains poorly understood. To understand the molecular pathogenesis of pancreatoblastoma, we comprehensively analysed the whole exome sequencing, RNA sequencing, SNP array, and methylation array data of pancreatoblastoma.

  Study JGAS000088

• DNA methylation at HBV integrants and flanking host genomes

  Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either the human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis.

  Study JGAS000015

• Aberrant (pro)renin receptor expression induces genomic instability by chromatin remodeler SMARCA5 disruption during the pancreatic ductal adenocarcinoma

  The aim of the present study is to elucidate whether aberrant (P)RR expression induces genomic instability in human pancreatic ductal epithelial (HPDE) cells, which are transforming into pancreatic ductal adenocarcinoma (PDAC).

  Study JGAS000143

• RNA-seq analysis of BMP-stimulated glioma initiating cells

  Bone morphogenetic protein (BMP) signaling has been shown to suppress progression of glioblastoma by promoting astrocytic differentiation; however, roles of BMP signaling in cell proliferation and apoptosis of glioblastoma cells remains to be elucidated. We here performed RNA-seq analysis of glioma initiating cells to identify transcriptional target(s) of BMP.

  Study JGAS000077

• Sequencing cancer mutations in various types of lung cancer using the long-read, portable sequencer

  In this study, we used a long-read and portable sequencer MinION to identify cancer mutations in lung adenocarcinoma cells. We performed cDNA amplicon sequencing for various types of mutations such as point mutations in EGFR and KRAS and oncogenic fusion transcripts in ALK and RET. Using the long reads of MinION, we also conducted mutation phasing of EGFR TKI-sensitive and resistant mutations, which would provide useful information to next thrapeutic approaches for cancers. We applied this method to identify mutation genotypes of eight clinical samples from Japanese lung adenocarcinomas. This method could provide new sequencing-based diagnostic approaches for lung cancers. Additinally we also performed cancer mutation identification of risk-dependent unique samples. Usual interstitial pneumonia (UIP) is a risk factor for lung carcinogenesis. This study was performed to characterize mutagenesis and mutational target genes underlying lung carcinogenesis in patients with UIP.We performed whole exome sequencing of lung adenocarcinoma with usual interstitial pneumonia.

  Study JGAS000065

• High-coverage whole exome sequence in non-TRU-type lung adenocarcinomas

  In order to elucidate the key genetic events in non-TRU-type lung cancer, we selected 43 non-TRU-type lung adenocarcinomas and performed a whole exome sequence and RNA-seq analysis using a next-generation sequencer. The results of the analysis identified mutations in TP53, KRAS and NKX2-1 as the top three significantly mutated genes, while the EGFR mutation was rare in this cohort. Eight NKX2-1 mutations (5 frameshift, 2 nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1 mutations (missense and frameshift). All NKX2-1 mutants were transcriptionally inactive in reporter assays. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1 mutations (5 cases), while 1 enteric and 1 acinar adenocarcinoma harbored the NKX2-1 mutation.

  Study JGAS000105

• Genomic subtypes and cellular phenotypes of high-grade endometrial carcinoma

  Based on the mechanism of carcinogenesis, endometrial cancer (EC) is classified into two major types, Type I and Type II. Type I EC is characterized by G1/G2 histology, accounting for about 80% of all uterine carcinomas. On the other hand, Type II EC, which often develops after menopause, is estrogen-independent and consists of serous and clear cell carcinomas. G3 EC is often classified as a Type II EC, but the pathogenesis is thought to be a mixture of estrogen-dependent and estrogen-independent carcinogenesis. We will conduct an integrative genomic analysis to clarify the pathogenesis of Type II EC and redefine its classification by combining genomic status with cell phenotypes reflected in gene expression profiles.

  Study JGAS000753

• Whole exome sequencing of uterine adenomyosis

  Uterine adenomyosis, defined by proliferation of the ectopic endometrial glands in myometrium, is a common benign uterine disorder that significantly impairs the quality of life of the women it affects. Adenomyosis lesions have chronic inflammatory reactions as well as cancer-like features such as invasive capacity into the normal myometrium. In contrast to endometriosis and leiomyoma, the genomic characterization of adenomyosis has yet to be reported. We conducted high-coverage whole exome sequencing analyses of freshly frozen adenomyosis samples, as well as co-occurring leiomyoma. Our WES analyses showed that adenomyosis is a clonal disorder with somatic mutations.

  Study JGAS000169

• Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma

  Myasthenia gravis (MG) is a neurological disease caused by autoantibodies against neuromuscular-associated proteins. While MG is frequently developed in thymoma patients, the etiologic factors for MG are not well understood. Here, by constructing a comprehensive atlas of thymoma using bulk and single-cell RNA-seq, we identified ectopic expression of neuromuscular molecules in MG-associated thymoma (MG-thymoma). These molecules were originated from a distinct subpopulation of medullary thymic epithelial cells (mTECs), which we named neuromuscular mTECs (nmTECs). MG-thymoma also exhibited microenvironments dedicated to autoantibody production, including ectopic germinal center formation, T follicular helper cell accumulation, and type 2 conventional dendritic cell migration. Cell-cell interaction analysis also predicted the interaction between nmTECs and T/B cells via CXCL12-CXCR4. The enrichment of nmTECs presenting neuromuscular molecules within MG-thymoma was further confirmed by immunohistochemically and by cellular composition estimation from MG-thymoma transcriptome. Altogether, this study suggests that nmTECs play a significant role in MG pathogenesis via ectopic expression of neuromuscular molecules.

  Study JGAS000482