16787 results for "sec+and+unspecified+malignant+neoplasm"

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• MAP Kinase-Mutant Hematologic Malignancies and Their Therapeutic Resistance

  The Mitogen-Activated Protein Kinase (MAPK) signaling pathway has been critically important in understanding pathology and developing targeted therapy for many cancers, but high frequency mutations in this pathway in hematopoietic malignancies were unknown until a series of sequencing studies from our group and others revealed a high frequency of activating mutations in BRAF (GeneID:673), MAP2K1 (GeneID:5604), and other key components of the MAPK pathway in two groups of rare and poorly studied blood cancers: hairy cell leukemia (HCL) and the systemic histiocytoses (SH). Although HCL and the SH both share common gene mutations in BRAF (BRAFV600E) and MAP2K1, these are distinct blood cancers with different clinical behaviors; however, their actual developmental cellular origins, genomic, and pathogenic differences are poorly understood, which led to our project goal of determining how BRAFV600E, MAP2K1, and other MAPK pathway mutations contribute to the pathogenesis of distinct blood cancers and affect their clinical responses to MAPK pathway inhibitors. This study proposal seeks to advance our understanding of the actual cells of origin of cancer-causing MAPK mutations in HCL and the SH, to determine why BRAFV600E and MAP2K1 mutations can cause two distinct blood cancers, and to understand how these mutations in HCL and SH influence responses to MAPK pathway inhibitor drugs and other receptor tyrosine kinase (RTK) inhibitors such as RET and ALK inhibitors that could potentially become effective therapy for these poorly understood blood cancers.

  Study phs001864

• OncoArray: Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)

  The Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) was one of five projects funded in 2010 as part of the NCI's Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (http://epi.grants.cancer.gov/gameon/). FOCI represents a collective effort that builds upon the strengths and history of collaboration inherent in the Ovarian Cancer Association Consortium (OCAC), a multidisciplinary group comprised of epidemiologists, genetic epidemiologists, statistical geneticists, molecular and cell biologists and clinicians that was formed in 2005. The other four funded GAME-ON projects were: the ColoRectal TransdisciplinaryStudy (CORECT), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), and Transdisciplinary Research in Cancer of the Lung (TRICL). As part of our aim to discover, expand, and replicate ovarian cancer susceptibility loci, the GAME-ON projects and other consortia formed the OncoArray network (http://epi.grants.cancer.gov/oncoarray/) to develop and genotype a new custom genotyping array in large numbers of cancer cases and controls (over 400,000 samples) across multiple cancer types. The FOCI data includes over 50,000 ovarian cancer cases and controls genotyped with the Oncoarray at the Center for Inherited Disease Research (CIDR). Genotype calling and quality control procedures were performed under a standardized protocol across the Oncoarray consortium, and over 490,000 SNPs passed QC and are included under this dbGaP submission.

  Study phs001882

• Preeclampsia InterPregGen Consortium: Whole Genome Sequencing of 100 unrelated Kazakhs (DNA samples from the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan; Gulnara Svyatova, Principal Investigator

  Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001000417 study data is whole genome sequencing of 100 unrelated Kazakhs in order to impute genotypes into PE cases and controls from Kazakhstan and to provide genetic data and infrastructure for future genetic studies in Kazakhstan and Central Asia more generally and to fill a gap in worldwide information as Central Asia is not adequately represented in available genomic data. This study is one component of the InterPregGen FP7 project. DNA samples for this component were collected by InterPregGen Consortium collaborators at the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan (Gulnara Svyatova, Principal Investigator)

  Study EGAS00001000417

• Monosomy 7 delineates a primitive acute myeloid leukemia with adverse prognosis and responsiveness to epigenetic therapy

  The mechanistic basis for adverse risk associated with monosomy 7 remains undetermined in AML. In contrast to del(7q), monosomy 7 conferred adverse prognosis independent of TP53 and complex karyotype. Single-cell RNA and ATAC-seq revealed an epigenetically remodeled landscape and expansion of multipotent progenitor (MPP)-like cells. Monosomy 7 derived progenitors were distinguished by reduced chromatin accessibility and expression of STK17A and NT5C3A, which conferred resistance to cytotoxic and venetoclax-based therapy. To circumvent resistance mediated by monosomy 7 and deficient TP53, histone deacetylase inhibitors (HDACi) effectively restored apoptotic potential and augmented the activity of venetoclax. In a randomized clinical trial including older unfit patients with AML and monosomy 7, responses were observed in the majority that received low-dose cytarabine, venetoclax and the HDACi pracinostat, some with durable remissions exceeding 3 years. Longitudinal studies highlighted diminution of MPP-like cells, linking epigenetic remodeling to clinical response and therapeutic vulnerability of monosomy 7 AML.

  Study EGAS50000001641

• Methylome sequencing of cell-free DNA and RRBS of solid tissue

  Early cancer detection by cell-free DNA (cfDNA) faces multiple challenges: low fraction of tumor cfDNA, molecular heterogeneity of cancer, and sample sizes not sufficient to reflect diverse patient population. We develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of cfDNA methylome (with >12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our system to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, thereby permitting the classification models to learn new features as training cohorts grow, and expanding their scope to other cancer types.

  Study EGAS00001006020

• Immunoprotective mechanisms and microbiota interplay in Salmonella Typhi infection

  Vaccine development against Salmonella enterica serovar Typhi (S. Typhi) requires a better understanding of interaction between human host and the resident microbial consortia in gastrointestinal tract. Healthy adult volunteers received either Ty21a, M01ZH09 or placebo, and underwent challenges with wt S. Typhi. Stool samples were collected at the screening interview (Baseline 1), prior to the first vaccination visit (Baseline 2), during vaccination (Day -28 and -26 for placebo and M01ZH09 groups; Day -32, -30, -28, -26 for Ty21a group), prior to challenge with S. Typhi (Day 0), and after challenge (day 0 12h, day 1, day 3, day 7, and day 10). 16S rRNA and messenger RNA were extracted from stool and sequenced on the Illumina Miseq and HiSeq 2000 platforms, respectively.

  Study phs001521

• Proteomic measurements in BioBank Japan

  The BioBank Japan (BBJ) is a biobank established in the Institute of Medical Science, the University of Tokyo to collect clinical information and biological materials (DNA and serum samples). It collected about 200 thousand participants of 47 diseases started in 2003 (BBJ 1st cohort), and 67 thousand participants of 38 diseases started in 2013 (BBJ 2nd cohort), both in collaboration with 12 medical centers through the MEXT and AMED's "The BioBank Japan Project." This project is aiming at further utilization of the materials, and clinical and genomic information managed by BBJ to contribute to precision medicine by storing, managing, and providing the materials and data, as well as identifying biomarkers associated with disease risk, prognosis, and drug sensitivity.

  Study JGAS000785

• Biobank Japan genotype data

  The BioBank Japan (BBJ) is a biobank established in the Institute of Medical Science, the University of Tokyo to collect clinical information and biological materials (DNA and serum samples). It collected about 200 thousand participants of 47 diseases started in 2003 (BBJ 1st cohort), and 67 thousand participants of 38 diseases started in 2013 (BBJ 2nd cohort), both in collaboration with 12 medical centers through the MEXT and AMED's "The BioBank Japan Project." This project is aiming at further utilization of the materials, and clinical and genomic information managed by BBJ to contribute to precision medicine by storing, managing, and providing the materials and data, as well as identifying biomarkers associated with disease risk, prognosis, and drug sensitivity.

  Study JGAS000412

• Biobank Japan genotype data

  The BioBank Japan (BBJ) is a biobank established in the Institute of Medical Science, the University of Tokyo to collect clinical information and biological materials (DNA and serum samples). It collected about 200 thousand participants of 47 diseases started in 2003 (BBJ 1st cohort), and 67 thousand participants of 38 diseases started in 2013 (BBJ 2nd cohort), both in collaboration with 12 medical centers through the MEXT and AMED's "The BioBank Japan Project." This project is aiming at further utilization of the materials, and clinical and genomic information managed by BBJ to contribute to precision medicine by storing, managing, and providing the materials and data, as well as identifying biomarkers associated with disease risk, prognosis, and drug sensitivity.

  Study JGAS000541

• Gastric_Mutational_Signatures__GMS_

  This study aims to characterise the mutation burdens and signatures of adult stem cells derived from different regions of the stomach in order to gain insight into the causes and preclinical evolution of the diverse cancer subtypes. Clonal populations of cells from different anatomical locations of the stomach will be derived through organoid culture and/or laser microdissection and interrogated by whole genome sequencing and/or targeted pulldown. A total of circa 300 samples from 20 – 30 donors (cancer and non-cancer patients undergoing total/partial gastrectomy) will be analysed for mutational burden and signatures and genomic findings correlated with topology, age, risk factors and different stages of pre-neoplastic or neoplastic progression.

  Study EGAS00001002939