16815 results for "sec+and+unspecified+malignant+neoplasm"

in 15.13 milliseconds.

• A Natural History Study of CMT1B, CMT2A, CMT4A and CMT4C

  Charcot Marie Tooth disease (CMT) is an umbrella term that covers any inherited peripheral neuropathy. People with CMT have a problem with the nerves that go to the feet and hands that cause muscle and sensation loss, as well as difficulty with balance. There are at least forty genes that, when mutated, cause CMT. The purpose of this study is to look at the natural history of CMT to see how it changes over time. Particular emphasis will be put on studying people with CMT1B, CMT2A, CMT4A, and CMT4C, though all people with CMT are encouraged to participate. Participants are invited back on a yearly basis to determine how the changes are occurring. Objectives: Determine the natural history and genotype-phenotype correlations of disease-causing mutations in CMT1B, CMT2A, CMT4A and CMT4C as well as other forms of CMT Determine the capability of the newly developed CMTPeds score and the Minimal Dataset to measure impairment and perform longitudinal measurements in patients with multiple forms of CMT over a ten-year window This is a longitudinal study of individuals with CMT. Study participants will be invited to be re-evaluated every year. Evaluations will consist of neurological histories and examinations, selected nerve conduction studies (NCS) as well as completion of assorted clinical outcome measures including the CMTNS, Minimal Dataset, and Peds CMT Scale. Selected CMT patients and controls will also receive glabrous skin biopsies.

  Study phs001419

• Detection and Targeting of Splicing Deregulation in Pediatric Acute Myeloid Leukemia Stem Cells

  This study evaluates the gene expression and splicing changes between pediatric patients with and without Acute Myeloid Leukemia (AML) and pediatric and adult patients with AML. We obtained bone marrow or peripheral blood from patients and isolated CD34+ stem and/or progenitor cells from pediatric patients with AML (10) or without AML (6) and adult patients with AML (5). In parallel, a targeted analysis for known, deleterious, genetic mutations in the KRAS, NRAS, and KMT2C genes identified 2, 5, and 6 AML patients with alterations, respectively. Additionally, Tapestri analysis further identified a mutation in the intronic region of the SF3B1 gene in multiple pediatric AML patients. RNA-Seq was performed on the purified cell populations at The Scripps Research Institute Next Generation Core on an Illumina NextSeq 500 sequencer with 150bp paired-end reads.These datasets revealed that, similar to adult AML, pediatric AML samples were enriched for Leukemia Stem Cells (LSC) markers. A deeper analysis showed widespread dysregulation of splicing in pediatric AML samples compared to age-matched non-leukemic samples. In addition, the splicing regulator RBFOX2 was downregulated with an accompanying increase in specific CD47 splice isoforms in the pediatric AML samples. Thus, the increased presence of LSCs in pediatric AML is possibly driven by global splicing deregulation, and the treatment with splicing modulators like Rebecsinib has a potential therapeutic value for eradicating LSCs in these patients.

  Study phs003196

• Performance comparison of three DNA extraction kits on human whole-exome data from formalin-fixed paraffin-embedded normal and tumor samples

  We generated 42 human whole-exome sequencing data sets from fresh-frozen (FF) and FFPE samples. These samples include normal and tumor tissues from two different organs (liver and colon), that we extracted with three different FFPE extraction kits (QIAamp DNA FFPE Tissue kit and GeneRead DNA FFPE kit from Qiagen, Maxwell\textsuperscript{TM} RSC DNA FFPE Kit from Promega). Variant calling analysis shows a very high rate of concordance between matched FF / FFPE pairs and equivalent performance for the three kits we analyzed. We find a significant variation in the difference of total number of variants called between FF and FFPE samples for the three different FFPE DNA extraction kits. Coverage analysis shows that FFPE samples have less good indicators than FF samples, yet the coverage quality remains above accepted thresholds. We detect limited but significant variations in coverage indicator values between the three FFPE extraction kits. Globally, the GeneRead and QIAamp kits have better variant calling and coverage indicators than the Maxwell kit on the samples used in this study, although this kit performs better on some indicators and has advantages in terms of practical usage. Taken together, our results confirm the potential of FFPE samples analysis for clinical genomic studies, but also indicate that the choice of a FFPE DNA extraction kit should be done with careful testing and analysis beforehand in order to maximize the accuracy of the results.

  Study EGAS00001002631

• DNA hypermethylation and differential gene expression associated with Klinefelter syndrome

  The molecular basis for the phenotypic traits and morbidity in Klinefelter syndrome (KS) are not clarified. As DNA methylation affect gene expression and thereby play a role in disease susceptibility, we performed genome-wide DNA methylation profiling of leucocytes from peripheral blood samples from 67 KS patients, 67 male controls and 33 female controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS patients, 9 control males and 13 female controls. Characterization of the methylome as well as the transcriptome of both coding and non-coding genes identified a unique epigenetic and genetic landscape of both autosomal chromosomes as well as the X chromosome in KS. A subset of genes show significant correlation between methylation values and expression values. Gene set enrichment analysis of differentially methylated positions yielded terms associated with well-known comorbidities seen in KS. In addition, differentially expressed genes revealed enrichment for genes involved in the immune system, wnt-signaling pathway and neuron development. Based on our data we point towards many new candidate genes (AKAP17A, AMOT, APOB, DACT1, DDX58, DOCK7, EIF2S3, FIGNL1, G3BP1, HENMT1, HERC5, IFI44, IFI44L, IFIT1, IFIT3, ISG15, KANK1, LGALS1, NSD1, PEX10, PLSCR1, RSAD2, SHROOM2, SLC25A6, SPEG, SPON2, TXLNG), which may be implicated in the phenotype and further point towards non-coding genes (RP13-216E22.4, RP13-36G14.4, G087825, G088512), which may be involved in X chromosome inactivation in KS and in the regulation of escape genes.

  Study EGAS00001002797

• Partner-independent fusion gene detection by multiplexed CRISPR/Cas9 enrichment and long-read Nanopore sequencing

  Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment possibilities. The promiscuity of fusion genes with respect to partner choice and exact breakpoint-positions restricts their detection in the diagnostic setting, even for known and recurrent fusion gene configurations. To accurately identify these gene fusions in an unbiased manner, we developed FUDGE: a FUsion gene Detection assay from Gene Enrichment. FUDGE couples target-selected and strand-specific CRISPR/Cas9 activity for enrichment and detection of fusion gene drivers (e.g. BRAF, EWSR1, KMT2A/MLL) - without prior knowledge of fusion partner or breakpoint-location - to long-read Nanopore sequencing. FUDGE encompasses a dedicated bioinformatics approach (NanoFG) to detect fusion genes from Nanopore sequencing data. Our strategy is flexible with respect to target choice and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in a single sequencing run. We observe on average a 508-fold on-target enrichment and identify fusion breakpoints at nucleotide resolution - all within two days. We demonstrate that FUDGE effectively identifies fusion genes in cancer cell lines, tumor samples and on whole genome amplified DNA irrespective of partner gene or breakpoint-position in 100% of cases. Furthermore, we show that FUDGE is superior to routine diagnostic methods for fusion gene detection. In summary, we have developed a rapid and versatile fusion gene detection assay, providing an unparalleled opportunity for pan-cancer detection of fusion genes in routine diagnostics.

  Study EGAS00001003964

• Genetic Studies of Chronic Kidney Disease (CKD)

  The Genetic Studies of Chronic Kidney Disease (CKD) is an ongoing genetic research and biobanking protocol which aims to elucidate the genetic basis CKD. The study recruits patients seen at the Columbia University Medical Center (CUMC) Nephrology Division for the evaluation and care of CKD. All patients clinically diagnosed with CKD are eligible to participate; there are no inclusion or exclusion criteria related to age, sex/gender, and/or race/ethnicity. In addition to office visits, patients are recruited in contexts including perinatal care and nonprofit events for patients with various forms of CKD; recruitment tools include bilingual informational brochures, flyers, and consent forms. All individuals provide informed consent; for minors, signature of the parent/guardian is required. Consent includes: use of biosamples given for genetic studies, and the request to be re-contacted if medically actionable genetic findings are identified. In the case of the latter, such research-level findings are first validated in a clinically certified (CLIA) laboratory environment, using a second sample given by the individual at the time of re-contact; following CLIA validation, the individual is once again re-contacted, and, assuming he or she still desires return of these results, they can then be returned. Following the above consent process to participate in the study, individuals provide a single biosample (generally, a venous blood sample), from which DNA is extracted using standard protocols and used for genetic studies, such as exome sequencing. Basic clinical and demographic data, including sex/gender, age, and race/ethnicity are also collected. All data collected is stored in a secure computerized database, with patient samples anonymized using numerical identifiers; the relation of this identifier to patients' names is kept in a locked computer file in a centralized database. Electronic data complies with all HIPAA and other privacy and security regulations, and resides on a firewall server maintained by the CUMC IT department.

  Study phs001828

• Effect of the Placental Transcriptome on Stunting in a Longitudinal African Cohort

  Mammals with placentas and flowering plants evolved genomic imprinting in nutritive tissues, the placenta and endosperm, respectively. In these tissues, the genomes inherited from the mother and father are in conflict over resource allocation to offspring. In imprinted genes, transcription is repressed on the paternal or the maternal allele, resulting in allele specific expression (ASE). We investigated the variation in ASE of imprinted genes in term human placentas in order to detect loss of imprinting (LOI), which leads to partial expression of the repressed allele. We collected the placental tissue from birth to women in our multigenerational, prospective cohort study in Mali, West Africa. We followed the women from their own infancies, early childhood to adulthood (age 18+ years). Contingent on prior informed consent, we collected placental tissue and umbilical cord tissue. We conducted RNA-Seq of the fetal compartment of the placentas and targeted DNA-Seq of the umbilical cord tissue, which is fetal, and of saliva samples from parents. Our sequencing effort produced two datasets. The first dataset is the whole transcriptome RNA-Seq dataset of 111 biopsies (59 placentas) and genotyping of 96 genes. Birth length, weight, and placental weight for the children associated with this dataset are listed in the phenotype file (DOI: 10.1093/molbev/msz226). The second dataset includes targeted RNA-Seq of 262 samples (251 placentas) and targeted DNA-Seq for 766 genes. The genes were selected because they met any one of the following criteria: (1) imprinted and reported in some studies, (2) highly expressed in placenta, or (3) relevant to diseases of interest in this cohort (https://doi.org/10.1093/g3journal/jkab176). This study provides the first systematic analysis of variation in LOI across genes and individuals in a human population, and should shed light on the hypothesis that the modulation of imprinting is an epigenetic mechanism and plays a role in the regulation of offspring growth.

  Study phs001782

• Shanghai Breast Cancer Genetics Study (SBCGS)

  The Shanghai Breast Cancer Genetics Study (SBCGS) includes data from four population-based studies conducted among Chinese women in urban Shanghai: the Shanghai Breast Cancer Study (SBCS), the Shanghai Breast Cancer Survival Study (SBCSS), the Shanghai Women's Health Study (SWHS), and the Shanghai Endometrial Cancer Study (SECS, contributing controls only). Shanghai Breast Cancer Study (SBCS): The SBCS is a population-based, case-control study conducted in urban Shanghai. Subject recruitment in the initial phase of the SBCS (SBCS-I) was conducted between August 1996 and March 1998. The second phase (SBCS-II) of recruitment occurred between April 2002 and February 2005. Breast cancer cases were identified through the population-based Shanghai Cancer Registry and supplemented by a rapid case-ascertainment system. Controls were randomly selected using the Shanghai Resident Registry. Approximately 3500 cases and 3500 controls were recruited in the study. Shanghai Breast Cancer Survival Study (SBCSS) and Shanghai Endometrial Cancer Study (SECS): The SBCSS also used the population-based Shanghai Cancer Registry to identify newly diagnosed breast cancer cases. A total of 5,046 breast cancer patients were recruited. In-person interviews were conducted to collect information on known breast cancer risk factors and anthropometrics by using protocols and questionnaires similar to those used in the SBCS. For genetic studies, controls for the SBCSS cases came from the SECS, which recruited healthy women between January 1997 and December 2003. With the exception of a few questions related specifically to breast or endometrial cancer risk, the questionnaires used in the SECS and the SBCS were very similar. Shanghai Women's Health Study (SWHS): The SWHS is a population-based prospective cohort study of approximately 75,000 adult women who were recruited between 1997 and 2000. The cohort has been followed by a combination of record linkage and active follow-ups. Breast cancer patients identified in the SWHS and non-cases were included in the current study.

  Study phs001088

• Polycystic Ovary Syndrome (PCOS) Genetics

  PCOS is a complex genetic disease reflecting the interplay of susceptibility genes and environmental factors. The cardinal reproductive feature of the syndrome, hyperandrogenemia, appears to play a direct role in the pathogenesis of the associated metabolic abnormalities. Male as well as female first-degree relatives have reproductive and metabolic phenotypes including increased prevalence rates of type 2 diabetes (T2D), metabolic syndrome (MBS) and other risk factors for cardiovascular disease (CVD). Northwestern University (NU) investigators lead a team that has extensive experience in phenotyping PCOS and in the genetic analysis of complex diseases including genome-wide association study (GWAS). Together with an expert group of collaborators from the Hershey Medical Center, and The University of Chicago, we have conducted a GWAS to identify PCOS susceptibility alleles using a large cohort of extensively and consistently phenotyped PCOS cases. Population controls for this study come from the NUgene project described below. NUgene project: In 2002, Northwestern committed to the development of a DNA repository to serve as a platform for the identification and validation of genotype-phenotype associations that will impact healthcare. The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants' DNA samples are coupled with data from a questionnaire (2 versions were used, 1 before and 1 after February 2006, both are included) and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators.

  Study phs000368

• Shanghai Breast Cancer Genetics Study (SBCGS)

  The Shanghai Breast Cancer Genetics Study (SBCGS) includes data from four population-based studies conducted among Chinese women in urban Shanghai: the Shanghai Breast Cancer Study (SBCS), the Shanghai Breast Cancer Survival Study (SBCSS), the Shanghai Women's Health Study (SWHS), and the Shanghai Endometrial Cancer Study (SECS, contributing controls only). Shanghai Breast Cancer Study (SBCS): The SBCS is a population-based, case-control study conducted in urban Shanghai. Subject recruitment in the initial phase of the SBCS (SBCS-I) was conducted between August 1996 and March 1998. The second phase (SBCS-II) of recruitment occurred between April 2002 and February 2005. Breast cancer cases were identified through the population-based Shanghai Cancer Registry and supplemented by a rapid case-ascertainment system. Controls were randomly selected using the Shanghai Resident Registry. Approximately 3500 cases and 3500 controls were recruited in the study. Shanghai Breast Cancer Survival Study (SBCSS) and Shanghai Endometrial Cancer Study (SECS): The SBCSS also used the population-based Shanghai Cancer Registry to identify newly diagnosed breast cancer cases. A total of 5,046 breast cancer patients were recruited. In-person interviews were conducted to collect information on known breast cancer risk factors and anthropometrics by using a protocol and questionnaire similar to those used in the SBCS. For genetic studies, controls for the SBCSS cases came from the SECS, which recruited healthy women between January 1997 and December 2003. With the exception of a few questions related specifically to breast or endometrial cancer risk, the questionnaires used in the SECS and the SBCS were very similar. Shanghai Women's Health Study (SWHS): The SWHS is a population-based prospective cohort study of approximately 75,000 adult women who were recruited between 1997 and 2000. The cohort has been followed by a combination of record linkage and active follow-ups. Breast cancer patients identified in the SWHS and non-cases were included in the current study.

  Study phs000799