Identification of driver genes in uterine leiomyosarcoma: whole-genome sequencing
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Complete Genomics
ORGANISM(S): Homo sapiens
SUBMITTER: Bram Boeckx
PROVIDER: E-MTAB-5764 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Metastatic melanoma is an aggressive treatment-refractory malignancy. Recently, c-Kit mutations were discovered in certain mucosal melanomas. A clinical trial was initiated with the c-Kit inhibitor imatinib mesylate. The first treated patient experienced dramatic clinical improvement within days, followed by major responses by PET/CT four weeks later at all sites of metastatic disease. Several established mucosal melanoma cell lines exhibited imatinib sensitivity in a fashion correlating with c-Kit mutational status. Although c-Kit mutations are uncommon in cutaneous melanoma, they may arise in geographically distinct subsets for whom use of c-Kit targeted kinase inhibition should be considered in a rational therapeutic approach. Keywords: Whole genome copy number analysis Copy number analysis using high-density SNP arrays to investigate genetic gains and losses involved in the genesis of mucosal and cutaneous melanoma. GSE8164_raw_copy_number_calls.xls contains raw copy number calls generated by dChip (build 5/2007) for GIST, K008, K029, M34, MEL1, MEL40, M6, and 5 Affymetrix controls (copy number identity 2 i.e. normal), which are available on the HapMAP site.
2008-12-23 | E-GEOD-8164 | biostudies-arrayexpress
Project description:Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and 3 lung tumor/normal pairs (provisional dbGaP accession number; phs000299.v2.p1). Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers. Nineteen non-small cell lung cancer cell lines were assayed for genotype, copy number and LOH using Illumina Omni2.5-4 arrays, GenomeStudio V2011.1, and a modified version of the PICNIC (PMID 19837654) algorithm.
2012-09-26 | E-GEOD-40908 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-04-07 | E-GEOD-23056 | biostudies-arrayexpress
Project description:We used RNA sequencing to analyze transcript profiles of ten autopsy brain regions from ten subjects. RNA sequencing techniques were designed to detect both coding and non-coding RNA, splice isoform composition, and allelic expression. Brain regions were selected from five subjects with a documented history of smoking and five non-smokers. Paired-end RNA sequencing was performed on SOLiD instruments to a depth of >40 million reads, using linearly amplified, ribosomally depleted RNA. 12 thousand protein coding and 2 thousand lncRNA transcripts were detectable at a conservative threshold. Of the aligned reads, 52% were exonic, 34% intronic and 14% intergenic. A majority of protein coding genes (65%) was expressed in all regions, whereas ncRNAs displayed a more restricted distribution. Profiles of RNA isoforms varied across brain regions and subjects at multiple gene loci, with neurexin 3 (NRXN3) a prominent example. Allelic RNA ratios deviating from unity were identified in > 400 genes, detectable in both protein-coding and non-coding genes, indicating the presence of cis-acting regulatory variants. RNA sequencing identifies distinct and consistent differences in gene expression between brain regions, with non-coding RNA displaying greater diversity between brain regions than mRNAs. Numerous RNAs exhibit robust allele selective expression, proving a means for discovery of cis-acting regulatory factors with potential clinical relevance. Sequenced whole transcriptomes of 10 brain regions from 10 individuals, 5 smokers and 5 nonsmokers
2015-09-01 | E-GEOD-68559 | biostudies-arrayexpress
Project description:Little is known of the genetic architecture of cancer at the subclonal and single cell level or in the stem-like cells responsible for cancer clone maintenance and propagation. We have examined this issue in ALL in which ETV6-RUNX1 gene fuson is an early or initiating genetic lesion followed by a modest number of driver copy number alterations. By multiplexing FISH probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of sub-clones identified and a composite picture of sub-clonal architecture and putative ancestral trees assembled. Sub-clones in ALL have variegated genetics and complex, non-linear or branching evolutionary histories. CNA are independently and recurrently acquired in sub-clones of individual patients, and in no preferential order. Clonal architecture is dynamic and changes in the lead up to a diagnosis and in relapse. Leukaemic stem cells, assayed by transplantation in NOD/SCID IL2Rgamma deficient mice, are also genetically variegated, mirroring sub-clonal patterns. These findings have significant implications for the cancer stem cell concept, for interpretation of cancer genome data and for therapeutic targetting in cancer. Mononuclear cells were isolated at diagnosis of ALL for patient #3 and #7. Transplantation of 2 000 - 2 000 000 unsorted leukaemia cells was performed by intra-tibial injection into 7 - 14 week old NOD/SCID IL2Rgamma deficient mice. Mice were sacrificed when peripheral blood engraftment was >2%. An equivalent of 2 000 - 200 000 CD45 cells were used for serial transplantation. DNA was extracted from mononuclear cells at initial diagnosis and after second transplantation. Copy number analysis of Affymetrix 500K SNP arrays was performed in CNAG 3.0 for patients #3 and #7 at initial diagnosis and after second transplantation. Reference files were 9 samples from leukemia in remission.
2010-12-16 | E-GEOD-24412 | biostudies-arrayexpress
Project description:We report the gene expression profile of 8 metastatic castration resisistant prostate cancer samples analyzed by paired-end RNA-seq. We found evidence of extensive abnormal splicing as well as several novel fusion genes. Finally, we also observed several recurrent high-confidence somatic mutations. Paired-end RNA-seq by rRNA depletion
2014-09-06 | E-GEOD-50630 | biostudies-arrayexpress
Project description:Melanoma recurrence frequently occurs after a latency period of several years. In vivo studies demonstrated that tumor cells overcoming latency show a T cell-edited phenotype, suggesting a relevant role for CD8+ T cells in maintaining metastatic latency. Here, in a patient model of multiple recurrent lesions, we illustrate the genetic evolution of poorly immunogenic melanoma phenotypes, evolving in the presence of autologous tumor antigen-specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. HLA class I-negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed total T-cell resistance in both metastases originating from a shared chromosome 15q alteration and independently acquired focal B2M gene deletions. A third HLA class I-positive lesion developed in year 3 of stage IV disease. By HLA haplotype loss lesion-derived melanoma cells acquired resistance towards dominant T-cell clonotypes targeting early stage III tumor cells. Early disease melanoma cells showed a dedifferentiated MITFnegative phenotype, recently described to be associated with immunosuppression, in contrast to the MITFhigh phenotype of T cell-edited tumor cells from late metastases. In summary, our study demonstrates that tumor recurrences after long-term latency develop towards T-cell resistance by independent genetic events, suggesting a mechanism of T cell-driven genetic evolution of melanoma as a means to evade immune recognition and tumor immunotherapy. Genetic alterations lead to loss of tumor antigen presentation. Cell lines were generated from tumor material, differences in T cell recognition were observed and Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from the cell lines. SNP analysis of different melanoma cell lines obtained from one melanoma patient (4 cell lines from different metastasis of one patient with matching germline DNA).
2016-07-27 | E-GEOD-80736 | biostudies-arrayexpress
Project description:Phospholamban R14del mutazion (PLN-R14del) has been identified in a large family pedigree in which heterozygous carriers exhibited inherited dilated cardiomyopathy (DCM) and death by middle age. To better understand the causal link between the mutations in PLN and DCM pathology, we derived induced pluripotent stem cells from a DCM patient carrying the PLN R14del mutation. We showed that iPSC-derived cardiomyocytes recapitulated the DCM-specific phenotype and demonstrated that either TALEN-mediated genetic correction or combinatorial gene therapy resulted in phenotypic rescue. Our findings offer novel insights into the pathogenesis caused by mutant PLN and point to the development of potential new therapeutics of pathogenic genetic variants associated with inherited cardiomyopathies. Submitter confirms there are no patient privacy concerns with these data. iPSCs were derived from a female patient carrying a heterozygous mutation (R14del) in the PLN gene. Tree samples were analyzed: R14del-CMs (clone L2), corrected R14del-CMs (clone L2GC1) and corrected R14del-CMs (clone L2GC2)
2015-02-09 | E-GEOD-65762 | biostudies-arrayexpress
Project description:All cancers are diseases of the genome. A combination of somatic point mutations, focal amplifications and deletions, and chromosome level aberrations conspire to disrupt gene expression and the interplay between signaling pathways that control normal growth and tissue homeostasis. Here we investigate somatic copy number abberations in metastatic melanomas. A metastatic melanoma was assayed on Affymetrix SNP arrays to detect copy number abberations. 7 cutaneous melanomas as well as their matched control ( peripheral blood lymphocytes (PBL) or Epstein-Barr virus transformed lymphoblastoid cell lines ) and 2 control melanocytes were assayed on Illumina SNP arrays. 7 metastatic melanomas were hybridized on Agilent CGH arrays using donor matched control as reference.
2011-04-07 | E-GEOD-22928 | biostudies-arrayexpress
Project description:Chronic active B cell receptor (BCR) signaling, a hallmark of the ABC subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activates IkappaB kinase (IKK) and the classical NF-kappaB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-kappaB activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetic drugs target cIAP1/2 for destruction, and consequently suppress NF-kappaB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL. Four ABC DLBCL tumor biopsy samples and one ABC DLBCL cell line (YM) (n=5) were analysed for copy number gains using the Affymetrix Genome-Wide Human SNP 6.0 Array. CEL files are being made available through dbGaP
2016-09-01 | E-GEOD-73639 | biostudies-arrayexpress