12322 results for ""statistically+reactive"+taxa+in+microbial+community"

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• Genetic Study of Vascular Anomalies

  Vascular anomalies are malformations or tumors of the vasculature that can result in significant morbidity and mortality. Vascular anomalies are caused by germline or post-zygotic pathogenic variants in genes that regulate cell growth and vascular development. Complex or extensive vascular anomalies are often intractable despite interventions such as sclerotherapy, embolization, or surgery. In recent years, targeted therapy has played an increasingly crucial role in the management of these diseases. Identification of the molecular causes of vascular anomalies is essential to provide efficacious therapy; however, genetic profiling is often limited by difficulty obtaining affected tissues and limited sequencing depth. The lack of this information limits treatment options and the precision of targeted therapy, especially for primary complex lymphatic anomalies. To address these limitations, we have applied novel techniques, including analysis of unconventional samples such as endothelial cells isolated from lymphatic fluid and cell-free DNA, deep coverage exome sequencing, and unique molecular identifier ultra-deep targeted sequencing, in the molecular profiling of these diseases.

  Study phs003197

• Single-Cell Analysis of Human Adipogenesis

  The data in this study consists of RNA sequencing reads and read counts from single-cell and single-nuclei RNA sequencing experiments performed on two cell lines to investigate the transcriptional landscape of human adipogenesis in both the brown and white adipose tissue lineage. The two cell lines are human preadipocytes collected and isolated from a defined anatomical location in the neck of a single individual. This depot is known to harbor white adipose tissue (WAT) and brown adipose tissue (BAT). These white and brown preadipocytes were immortalized for the purposes of studying human adipogenesis in vitro. In this study we induced differentiation of these two preadipocyte lines and performed RNA sequencing on over 135,000 single cells spanning a 20-day time course from unperturbed preadipocytes to mature adipocytes from both brown and white lineages. Additionally, we performed both single-cell and single-nuclei RNA sequencing to comprehensively compare the advantages and disadvantages of either technique.

  Study phs002461

• A Whole Genome Association Scan for Myopia and Glaucoma Endophenotypes using Twin Studies

  Myopia and glaucoma are highly prevalent ophthalmic disorders worldwide and contribute significantly to ocular morbidity. There is substantial evidence that genetic factors play a significant role in the development of non-syndromic myopia and glaucoma. We propose to perform mapping studies for well-characterized twin populations in the United Kingdom and Australia in order to ultimately identify implicated genes for these disorders and related ocular parameters. This will provide a fundamental molecular understanding of how these disorders develop, and may lead to directed physiologic (i.e. pharmacologic, gene therapy) interventions. Our aim is to dissect the genetic basis of the eye disorders myopia and glaucoma. Instead of limited analyses of the trait/disease in a dichotomous manner, we are using continuous phenotypes of measures of refraction and intermediate phenotypes of glaucoma to analyze quantitative traits in unselected population samples of volunteer twins. Achievement of this goal requires cooperative efforts and large sample sizes. Thus, we have created an international collaboration of large complementary studies.

  Study phs000142

• Genomic Analysis of Paired Endometrial Cancer Primaries and Metastases

  Formation of metastases is the major cause of cancer related deaths. Recent studies have sequenced primary endometrial carcinomas yielding data for a single entity in the progression from the birth of a progenitor tumor cell to metastatic disease. However, the progression of these tumors to metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed TCGA-data, identifying novel recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor NRIP1 in 12% of patients. We found that likely driver events tended to be shared by primary and metastatic tissue-samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses in cases with multiple metastases indicated these metastases typically arose from one lineage of the primary tumor. These data indicate extensive genetic heterogeneity within endometrial cancers and relative homogeneity across metastatic sites.

  Study phs001127

• Sézary Syndrome Originates from Heavily Mutated Hematopoietic Progenitors

  The pathogenesis of cutaneous T cell lymphoma (CTCL) remains unclear. To study the malignant transformation of CTCL, we collected matched hematopoietic stem cell (HSC) extracts from bone marrow, CD4+CD26- malignant T cells, CD4+CD26+ normal T cells, and CD34+ HSCs from apheresis performed on 4 patients. To establish the baseline for calling true mutations without using hematopoietic cells, we also cultured bone marrow fibroblasts from each patient to use as normal controls. Whole exome sequencing (WES) was performed on all samples for somatic mutation calling. We identified >200 mutations in CD34+ HSCs derived from either bone marrow or apheresis. Previously reported key oncodrivers in Sezary Syndrome were identified in autologous HSCs and malignant peripheral cells, but not in progenitor (bone marrow HSCs) cells. Also, we identified specific mutations shared by autologous HSCs and malignant peripheral cells in every patient. WES data of bone marrow HSCs, apheresis HSCs, CD4+CD26- T cells, CD4+CD26+ T cells, and fibroblasts will be available through dbGaP.

  Study phs003158

• Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

  While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE [Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics] project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis.

  Study phs001703

• NHLBI TOPMed: MWCCS: Sex Differences in the Role of Multi-Omics in HIV-Associated Carotid Artery Atherosclerosis

  The MACS-WIHS Combined Cohort Study (MWCCS) is a multicenter prospective cohort study of men and women in the U.S. that aims to understand and reduce the impact of chronic health conditions, including heart, lung, blood, and sleep (HLBS) disorders that affect people living with HIV. MWCCS, which currently has over 5000 active study participants, is designed to investigate a spectrum of questions relating to the basic science, clinical science, and epidemiology of HIV infection in the U.S., with a focus on comorbidities among men and women living with HIV. The current substudy, nested within the MWCCS, integrates detailed metabolomics and proteomics data, among other "omics" measures, to improve the understanding of the etiology of atherosclerosis and cardiovascular disease in women and men with HIV, guide mechanistic studies, and provide insights to more efficient intervention strategies. Data on 374 men are included in the current substudy.

  Study phs003651

• Single-cell Analysis of Neoplastic Plasma Cells Identifies Myeloma Pathobiology Mediators and Potential Targets

  Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell (sc)RNA- with scB-cell receptor (BCR)-sequencing, we differentiate monoclonal/neoplastic from polyclonal/normal PCs, and find more dysregulated genes, especially in precursor patients, than by analyzing bulk PCs. To determine if this approach can identify oncogenes that contribute to disease pathobiology, MAD2L1 and MAT2A are validated as targets with drug-like molecules that suppress myeloma growth in pre-clinical models. Moreover, functional studies show a role of LAMP5, which is uniquely expressed in neoplastic PCs, in tumor progression and aggressiveness via interactions with c-MYC. Finally, a monoclonal antibody recognizing cell-surface LAMP5 shows efficacy as an antibody-drug conjugate and in a chimeric antigen receptor-guided T-cell format. These studies provide additional insights into myeloma biology and identify potential targeted therapeutic approaches that can be applied to reverse myeloma progression.

  Study EGAS50000000802

• Uncovering Gene Regulatory Differences between Human and Chimpanzee Neural Cells

  A major challenge in human evolutionary biology is to pinpoint the genetic differences that underlie phenotypic changes in the human lineage, such as increased neuron number and a prolonged period of neuronal maturation. Here, we used human-chimpanzee tetraploid cells to distinguish changes in gene expression due to cis-acting sequence variants that change local gene regulation, from trans expression changes due to species differences in the cellular environment, in neural progenitor cells and excitatory neurons using RNA-seq and ATAC-seq. Using a CRISPR inhibition screen with scRNA-seq, transcription factor motif analyses with CUT&Tag, and downstream single-locus studies with RNA-seq, we further characterized cis-acting gene regulatory differences, including changes to FOS, TNIK, FOSL2, and MAZ, that influence neurogenesis and neuronal maturation. This study identifies specific genomic changes that may contribute to human neural specializations and provides a general framework for understanding genetic differences that underlie human traits.

  Study phs004053

• Single cell RNA sequencing of human embryonic forebrain after slice culturing for between four weeks and one month

  With the aim of verifying normal tissue development in our Organotypic Timelapse recording with Transcriptomic Readout (OTTR) live tissue imaging method, we performed single cell RNA sequencing in organotypic slice cultures containing labelled cells from virally delivered ubiquitous Enhanced yellow fluorescent protein (EYFP)-expression. Human fetal cortices of PCW 7.5-10.5 were cut into strips along the dorso-ventral axis and directly placed en face, ventricular side down, on PTFE culturing membranes. To assess tissue health with our culturing method, we performed single cell RNA-seq analysis of the cortical explants (using adjacent slices from the same samples subjected to timelapse imaging). We cultured these control slices for four days in vitro (mimicking the start of a live imaging experiment after lentiviral infection and expression of EYFP), 11 days in vitro (corresponding to the end of one week of live imaging), and for two weeks and one month in vitro.

  Study EGAS50000001185

• Dynamic human admixture histories over the past ~1,300 years at the northern Himalayan frontier

  Archaeological and paleogenomic evidence from the Tibetan Plateau and high-altitude Central Himalayas suggest biocultural connections with each other and with lowland East, Central, and South Asia. However, genetic histories at the northern frontier of the Indian Himalayas, which is geographically more proximal to Central and lowland South Asia, remain underexplored. We analyzed genome-wide data from 7 ancient (~2300 to 100 years old) and 10 present-day individuals from the northern Indian Himalayas and one ~3370-year-old individual from the Central Himalayas in Nepal. Ancient and present-day individuals from the northern Himalayas predominantly have Tibetan-related genetic ancestry, likely the source of high-altitude adaptive variants in these individuals, with substantial Steppe-related genetic ancestry that is observed in all individuals dating between ~1300 years and present day. In addition, some present-day individuals have lowland South Asian admixture. Our analyses reveal a dynamic interplay between genetic admixture and continuity in the northern Himalayas.

  Study EGAS50000001342

• TONIC-Trial-cfDNA-Project

  Cell-free DNA (cfDNA) is an emerging technology to predict and monitor response to cancer treatment, including immune checkpoint blockade (ICB). However, data on cfDNA dynamics during ICB in metastatic triple negative breast cancer (mTNBC) are limited. While most applications of cfDNA involve assays that focus on mutation detection, mTNBC and multiple other cancer types are driven by copy number alterations (CNAs). We evaluate cfDNA-based copy number profile abnormality (CPA) score as a potential biomarker for monitoring ICB response in mTNBC, analyzing data from 87 patients enrolled in stage 1 and stage 2 of the TONIC-trial. We find significant concordance between cfDNA-based and tissue-based CNA profiles. Additionally, responders show a decrease in CPA scores upon ICB at week 6 (3 cycles of nivolumab). These findings underscore the potential of cfDNA-based CNA dynamics as a non-invasive biomarker for ICB early response assessment in patients with mTNBC.

  Study EGAS50000001308

• Single-cell Kinnex sequencing of Alzheimer's disease isoform profile

  Alzheimer’s disease (AD) is the most common cause of dementia, yet its molecular causes remain incompletely understood. RNA diversity in part arising from dysregulated splicing may contribute to AD pathogenesis; however, the ability to interrogate the resulting full-length isoforms in single brain cells has been technologically limited. Here we report the use of PacBio Kinnex long-read sequencing combined with 10X Genomics single-cell preparations to identify both annotated and unannotated RNA isoforms. Eight AD and seven non-diseased post-mortem human brains yielded ~70,000 single nuclei showing diverse, differentially expressed, and switched transcripts in multiple genes. Cell-type-specific isoform expression and variants with intra-exonic junctions associated with reverse transcriptase-mediated somatic gene recombination were also detected. Novel isoforms, including CHI3L1 and SEPTIN4, were altered in AD. Kinnex sequencing of RNA isoforms from single nuclei detected vast isoform diversity amongst brain cell types, representing an under-explored element in AD and other brain disorders.

  Study EGAS50000001476

• Common origin and somatic mutation patterns of composite lymphomas and leukemias

  When two lymphomas occur concurrently or sequentially in a patient, it is a major question whether they derive from the same lymphocyte or hematopoietic precursor cell or developed independently. We studied four composite classic Hodgkin lymphomas (HL) and other mature B-cell lymphomas, and two composite mature B- and T-cell neoplasias by whole exome sequencing (WES) and analyzed shared somatic mutations in the lymphomas of these clonally related composite lymphomas, indicating their derivation from a common, pre-malignant precursor. Most identified mutations were restricted to one or the other of these lymphomas, likely explaining how distinct lymphomas developed from a common ancestral B cell. In the two B-cell/T-cell lymphoma cases, and a composite clonally unrelated HL/chronic lymphocytic leukemia, the lymphoma partners did not share any somatic mutations. In three cases, we identified potentially oncogenic variants also in cells serving as constitutional controls.

  Study EGAS50000001017

• Measles oncolytic virus as an immunotherapy for recurrent/refractory pediatric medulloblastoma and atypical teratoid rhabdoid tumor

  Pediatric recurrent medulloblastoma (MB) and atypical teratoid rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. We investigated a) the safety of a measles virus variant, MV-NIS, in a pediatric phase 1 study and b) the mechanisms of MV-NIS and potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent MB or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model. MV-NIS given intratumorally or via repeat intrathecal dosing was safe. MV-NIS prolonged survival in murine models but did not demonstrate additive benefit with ICI. No changes in tumor-infiltrating immune-cell composition or activation were observed in response to MV-NIS treatment; however, MV-NIS induced local expression of neutralizing antibodies, complement cascade, and phagocytosis-related genes.

  Study EGAS50000000811

• Whole genome sequencing data for 10 hepatocellular carcinomas (HCC) and matched non-tumor liver tissues + optical mapping data for 4 HCC and 3 matched non-tumor liver tissues.

  Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole genome sequencing to explore in-depth the nature of structural variants (SVs) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC display frequent intra- and inter-chromosomal templated insertion cycles (TIC) likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are close in the 3D genome organization. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induces continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics and consequences of SV accumulation in tumors with oncogene-induced replication stress.

  Study EGAS00001005629

• Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients.

  Over the last decade, molecular stratification and associated therapies have greatly improved the treatment options and prognosis of patients diagnosed with breast cancer. However, metastatic disease remains incurable. Breast cancer cells mainly spread to the lung, liver, bone and brain and circulating tumor cells (CTCs) that migrate in the lymphatics or blood have been implicated as the cellular source of metastasis. Detailed molecular and functional characterization of patient CTCs remains poor due to their low number in patient’s bloodstream. In addition, CTCs are difficult to culture and expand ex vivo. Here we have established a novel method for culturing and unlimitedly expanding breast cancer patient-derived CTCs in CTC-derived organoids (CDOs). Our platform can serve as a foundation for serial longitudinal isolation and expansion of breast cancer cells from peripheral blood. This may enable the identification and functional validation of therapy resistance mechanisms during disease progression, which can be used for new approaches in precision medicine.

  Study EGAS00001007582

• Adult granulosa cell tumor WGS data cohort with corresponding reference germline WGS data

  Adult granulosa cell tumors (AGCTs) harbor a somatic FOXL2 c.402C>G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain  of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29-80% unique somatic mutations per sample, suggesting tumor heterogeneity. FOXL2-wildtype AGCTs had DICER1, TERT(C228T) and TP53 mutations and similar CNV profiles as FOXL2-mutant tumors. Our study confirms that absence of the FOXL2 c.402C>G mutation does not exclude AGCT diagnosis. The lack of overlapping variants in targetable cancer genes, indicates the need for personalized treatment for AGCT patients 

  Study EGAS00001004249

• Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia

  In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness, and poor patient outcomes. A later arrest was associated with lineage fidelity, deep and durable leukemia remissions, and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ pre-leukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI-efficacy is an unexpected outcome of the differentiation stage at which this leukemia transforms.

  Study EGAS00001007167

• Frequent alterations in cytoskeleton remodeling genes in primary and metastatic Chinese lung adenocarcinomas

  The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including themost commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scalesequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.

  Study EGAS00001000982

• A novel subset of human CD33+ haematopoietic stem cells characterized at single-cell resolution

  Elucidation of the identity and diversity of mechanisms that sustain long-term human blood cell production remains an important challenge. Previous studies indicate that, in adult mice, this property is ultimately vested in cells uniquely identified by their ability to clonally regenerate detectable levels of mature blood cells in serially transplanted recipients. We now present a combined multi-parameter analysis of the molecular features of very primitive human cord blood cells that display different cell output activities in vitro and in vivo. These analyses identified a new, prospectively separable, but still functionally heterogeneous, subset of long-term human blood-forming cells. Single-cell measurements of their transcriptional, DNA methylation and 40-protein content and of closely related phenotypes revealed numerous subtle, but consistent differences both within and between each subset analyzed. These results suggest that multiple regulatory mechanisms underlie the functional heterogeneity exhibited by clonally tracked human blood cell precursors with long-term output abilities.

  Study EGAS00001002826

• Next_gen_seq_of_eye_cancers

  Retinoblastoma (RB), the commonest eye cancer in children was the first cancer for which a genetic cause was identified: the Rb1 gene is a tumour suppressor gene that is mutated in RB. The Rb1 gene defect alone does not predict the clinical outcome. We propose to study other possible mechanisms: 1. Stepwise further mutations occur in RB, increasing its carcinogenesis. We will sequence the whole genome in RB tissue, and relate the different genes expressed to the treatments used. 2. Extracellular matric proteins contribute to a tumour permissive environment for RB to continue to grow. This includes Samll Leucine Rich Proteoglycans (SLRP), a family of 15 secreted extracellular matrix proteins involved in eye development. 3. Cancer stem cells (CSC), a subpopulation of treatment resistant cells, drive RB tumours, and whether these stem cells can be manipulated for new therapies. The aim of this study is to assist finding targeted diagnostic techniques and treatments for RB.

  Study EGAS00001002309

• Integrative genomic and transcriptomic analysis of adult leiomyosarcoma (HIPO-028, HIPO-018, HIPO-021)

  Leiomyosarcoma (LMS) is an aggressive mesenchmyal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. We performed genomic and transcriptomic profiling of a large cohort of LMS tumors and identified substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations, chromothripsis, and frequent whole-genome duplication. Furthermore, we discovered recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and RPA1, resulting in alternative lengthening of telomeres in 78% of cases. Finally, most tumors displayed hallmarks of “BRCAness”, including alterations in various homologous recombination DNA repair genes, multiple structural rearrangements, and enrichment of specific mutational signatures, and cultured LMS cells were sensitive towards olaparib and cisplatin treatment. This first comprehensive study of genetic alterations in LMS has uncovered key biological features that may inform future experimental research and enable the design of novel therapeutic strategies for this disease.

  Study EGAS00001002437

• Dynamics of neoantigen landscape during immunotherapy

  Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones. Peptides generated from the eliminated neoantigens elicited clonal T cell expansion in autologous T cell cultures, suggesting that they generated functional immune responses. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations and were associated with changes in T cell receptor clonality. These analyses provide insights into the dynamics of mutational landscapes during immune checkpoint blockade and have implications for development of immune therapies that target tumor neoantigens.

  Study EGAS00001002704

• Genome Landscape of High-Grade Serous Ovarian Cancer

  Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

  Study EGAS00001000397