3855 results for "*geneti*"

in 42.17 milliseconds.

• Exome sequencing of uterine leiomyosarcomas

  Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X-linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. Aberrant expression of both TP53 and ATRX were associated with poor overall survival. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS.

  Study EGAS00001001612

• Genetic Basis of Hepatosplenic T Cell Lymphoma (HSTL)

  Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown.  Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets.

  Study EGAS00001002182

• HipSci___Whole_Exome_sequencing___Kabuki

  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 Kabuki syndrome

  Study EGAS00001001981

• Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy

  Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits including cardiovascular diseases.Results: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 149 (97)* patients with dilated cardiomyopathy and 113 (108)* non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage and allele specific expression. Systematic annotation of genome wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome wide association signals in two independent cohorts.Conclusions: RNA transcription, splicing and allele specific expression are each important determinants of the DCM phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics. (*) numbers in parentheses represent samples that the publication is based on.

  Study EGAS00001002454

• HipSci_RNASEQ_Hypertrophic_Cardiomyopathy

  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 RNAseq on iPS lines from Hypertrophic Cardiomyopathy patients.

  Study EGAS00001001994

• Whole exome sequencing of Parkinson's disease patients from the United Kingdom

  As part of the International Parkinson's Disease Genomics Consortium, exomes of Parkinson's disease (PD) patients and healthy controls were sequenced to study the genetic etiology of PD. This UK cohort consists of 70 PD patients. Researchers can apply for access to fastq, vcf and binary plink files for this cohort.

  Study EGAS00001002156

• Genomic_profiling_of_B_other_Adult_ALL_WGS

  Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes. Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”. We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.

  Study EGAS00001002474

• Combined genetic and transcriptome analysis of patients with Systemic Lupus Erythematosus (SLE)

  A comprehensive profiling of the genomic architecture of Systemic Lupus Erythematosus (SLE) by combining genetic and transscriptomic analysis by RNA-seq.

  Study EGAS00001003662

• MeDALL epigenetics study

  MeDALL- (Mechanisms of the Development of ALLergy) is a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework programme (grant agreement number 261357).MeDALL epigenetics study includes illumina 450k methylation measurements from 4 cohorts: Infancia y Medio Ambiente (INMA), Etudes des Déterminants pré et postnatals précoces du développement et de la santé de l’ENfant (EDEN), Children’s Allergy Environment Stockholm Epidemiology study(BAMSE), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA)

  Study EGAS00001002169

• Genome-wide DNA methylation profiles of NSCLC xenograft and primary lung tissues for the identification of epigenetic predictive biomarkers.

  Non-small cell lung cancers (NSCLC) are the most common cause of cancer-related deaths worldwide and primarily treated with platinum-based drugs like cisplatin and carboplatin, radiation and surgery. The major challenge in the management of NSCLC are intrinsic or acquired resistance mechanisms with only few published molecular markers which can predict the outcome of the patients. On the other side, changes in DNA methylation are observed in nearly all cancer types making them suitable as biomarker. Here genome-wide methylation profiles from MeDIP-Seq and gene expression profiling data of 22 primary NSCLC, adjacent normal tissue and PDX samples are provided. For each PDX tumor growth rates were measured in absence or presence of chemotherapy.

  Study EGAS00001002479