4076 results for "*geneti*"

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• Genomics analysis of mucinous tumours of the ovary and related neoplasms

  To perform genetic and gene expression analyses on mucinous ovarian tumours to determine a progression model, cell of origin and novel therapeutic targets.

  Study EGAS00001003545

• Comprehensive Genomic and Transcriptomic Analysis of Rare Cancers for Guiding of Therapy (H021)

  Here we analyzed the molecular profiles and clinical outcomes of 1,310 patients (proportion of rare cancers, 75%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. Based on 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved response and disease control rates (23.9% and 55.3%, respectively) compared to previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients.

  Study EGAS00001004813

• BLUEPRINT ChIP-seq of Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity

  Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.

  Study EGAS00001000951

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD43291_Novaseq__WG_

  Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.

  Study EGAS00001003502

• Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants

  De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann-Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the detailed clinical information required to determine whether those individuals have isolated NDDs or WSS (i.e. syndromic NDDs). We performed thorough clinical and neurodevelopmental phenotyping on six individuals with de novo KMT2A variants. From these data, we found that all six patients met clinical criteria for WSS and we further define the neurodevelopmental phenotypes associated with KMT2A variants and WSS. In particular, we identified a subtype of Autism Spectrum Disorder (ASD) in five individuals, characterized by marked rigid, repetitive and inflexible behaviours, emotional dysregulation, externalizing behaviours, but relative social motivation. To further explore the clinical spectrum associated with KMT2A variants, we also conducted a meta-analysis of individuals with KMT2A variants reported in the published literature. We found that de novo LoF or missense variants in KMT2A were significantly more prevalent than predicted by a previously established statistical model of de novo mutation rate for KMT2A. Our genotype-phenotype findings better define the clinical spectrum associated with KMT2A variants and suggest that individuals with de novo LoF and missense variants likely have a clinically unrecognized diagnosis of WSS, rather than isolated NDD or ASD alone. This highlights the importance of a clinical genetic and neurodevelopmental assessment for individuals with such variants in KMT2A.

  Study EGAS00001003521

• The_contribution_of_POT1_variants_to_sporadic_melanoma_development

  A case-control series of melanoma cases from Leeds, UK have been sequenced in the Fluidigm platform to identify genetic variants associated with sporadic melanoma development. Samples in which potentially contributing variants have been detected are being sequenced in an orthogonal platform for variant confirmation.

  Study EGAS00001001964

• HipSci___Whole_Exome_sequencing___Battens

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease

  Study EGAS00001001975

• MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty___WG__Novaseq_

  Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (<20 to >60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.

  Study EGAS00001003524

• Growth Hormone (GH) -secreting Pituitary Adenoma

  We profiled the somatic landscape of 21 growth hormone (GH) -secreting pituitary adenomas using somatic copy-number alteration (SCNA), whole-genome sequencing (WGS), bisulfate sequencing, and transcriptome approaches. See details in Valimaki et al. Genetic and epigenetic characterization of growth hormone (GH) - secreting pituitary tumors. Manuscript in preparation, 2019.

  Study EGAS00001003488

• Mutational patterns and regulatory networks in epigenetic subgroups of meningioma (H033)

  DNA methylation patterns delineate clinically relevant subgroups of meningioma. We previously established the six meningioma methylation classes (MC) benign-1, 2, 3, intermediate-A, B and malignant. Here, we set out to identify subgroup-specific mutational patterns and pathway regulation. Whole-genome-sequencing was performed on 62 samples across all MCs and WHO grades from 62 patients with matched blood control, including 40 sporadic and 22 radiation-induced (Mrad) meningiomas. RNA sequencing was added for 18 cases and chromatin-immunoprecipitation for the enhancer mark H3K27ac followed by sequencing (ChIP-seq) for 16 samples. Besides the known mutations in meningioma, structural alterations were found to contribute to the spectrum of mechanisms inactivating NF2 in sporadic meningioma similar to previous reports for Mrad. Aberrations of DMD were found to be enriched in MCs with NF2 mutations and DMD was among the most differentially upregulated genes in NF2 mutant compared to NF2 wild-type cases. The mutational signature AC3 was detected in both sporadic meningioma and Mrad, but distributed across the genome in sporadic cases and enriched near genomic breakpoints in Mrad. In general, the malignant MC presented a significantly higher exposure to AC3 and higher genomic instability beyond the mutational load than the other MCs. Pathway analysis of the ChIP-seq clusters revealed that the FOXM1 is most differentially activated in high-grade cases, along with super enhancer recruitment near HOX genes and respective upregulation of expression. This data further elucidate the biological mechanisms differentiating meningiomas of different WHO grade and epigenetic subgroups and suggest leveraging the genomic instability as novel therapeutic targets.

  Study EGAS00001003481