21040 results for "fc 26 coins Buyfc26coins.com is EA Sports official for FC 26 coins The service is affordable and quick..JIZq"

in 32.77 milliseconds.

• Exploring the Genomic Dark Matter of Neurodevelopmental Disorders

  Neurodevelopmental Disorders (NDDs) are a group of disorders that typically manifest early in development and may give rise to impaired cognition, communication, adaptive behavior, and psychomotor skills. This study aims to take a more comprehensive view into the genomic landscape of structural variants implicated in NDDs with intellectual disability (ID). We have evaluated the genome of families with a genetically unsolved severe NDD via optical genome mapping. This study identified likely pathogenic or pathogenic structural variants in known NDD genes, including BCL11A, OPHN1, PHF8, SON, and NFIA. Data is available in VCF format, following the standard filtering settings in Bionano Access and available as "variants_combine_filters_inMoleRefine1.vcf" files.

  Study phs002937

• Small_molecule_inhibitors_in_melanoma___Kenski___Kong___WES

  Small-molecule inhibitors targeting the most commonly activated pathway in melanoma, MAPK pathway (either alone or in combination) are already given to melanoma patients for few years, and initially reduce tumour burden dramatically, eventually melanomas become resistant and tumours progress while on treatment. Resistance to this treatment occurs by acquisition of additional mutations or other alterations that affect the mitogen-activated protein kinase (MAPK) pathway by either direct or indirect signalling. Many resistance mechanisms somehow lead to reactivation of extracellular signal-regulated kinase (ERK), thereby restoring signalling of the oncogenic BRAF/MEK/ERK pathway. In addition, PI3K pathway activation contributes to resistance to BRAF inhibition. Less frequent but equally important to the phenomenon of targeted drug resistance is the observation that B15–20% of BRAF mutant melanoma patients fail to respond to BRAF inhibition already early on treatment, owing to intrinsic resistance. These patients have little therapeutic options, unless immunotherapy can be given. To better understand the resistance mechanisms in MAPK inhibitor-treated melanoma patients and melanoma biology, our lab generated a big panel of MAPK inhibitor resistant melanoma cell lines by continuous drug exposure. The understanding of the genetic landscape and gene expression as well as cross resistance to other treatment regimens, and other aspects of melanoma biology such as phenotype switch, will allow us to better exploit new therapeutic strategies for melanoma patients.

  Study EGAS00001002863

• Swarm Learning to identify COVID-19, tuberculosis and leukemia patients based on blood transcriptomes

  Identification of patients with life-threatening diseases including leukemias or infections such as tuberculosis or COVID-19 is an important goal of modern precision medicine. However, there is an increasing divide between what is technically possible and what is allowed because of privacy legislation. We have recently illustrated that classical machine learning can identify leukemia patients based on their blood transcriptomes. To facilitate integration of any omics data from any data owner world-wide without violating privacy laws, we here introduce Swarm Learning (SL), a decentralized machine learning approach uniting edge computing, artificial intelligence (AI), blockchain and privacy protection without the need for a central coordinator thereby going beyond federated learning. To illustrate its feasibility, using more than 12,000 transcriptomes from peripheral blood mononuclear cells and more than 2,000 peripheral blood transcriptomes we demonstrate that SL of omics data distributed across different individual sites leads to disease classifiers that outperform those developed at individual sites. Yet, SL completely protects local privacy regulations by design. We propose this approach to noticeably accelerate the introduction of precision medicine.

  Dataset EGAD00001006231

• Common early-life exposure of the colorectal epithelium to the microbiome-derived mutagen colibactin

  Colibactin is a mutagen produced by bacterial strains in the colorectal microbiomes of some healthy people. It generates somatic mutations characterised by the mutational signatures SBS88 and ID18 in normal human colorectal epithelial cells in vivo. Increasing prevalence of colibactin mutagenesis during the 20th century is hypothesised to have caused recent international increases in early-onset colorectal cancer incidence. Here, we establish the early-life prevalence, timing, mutation burdens and distribution through the colon of colibactin mutagenesis by sequencing normal colorectal epithelial cell genomes to detect SBS88 and ID18 in children and adolescents from the UK and Denmark biopsied between 2016 and 2024. Colibactin mutagenesis was found in ~40% individuals. It starts soon after birth and often ceases by age five years, although some children show longer exposures. Mutation burdens are higher in the left than right colon and show substantial variation between exposed individuals, in some causing >100-fold increases in total mutation loads compared to unexposed children of the same age. Therefore, colorectal mutagenesis by colibactin is currently common in some populations, occurs during early childhood and can produce markedly elevated somatic mutation burdens. The future public health implications of this widespread mutagen exposure will depend on clarification of its role in colorectal cancer causation.

  Dataset EGAD00001015830

• Monitoring of leukemia clones in B-cell acute lymphoblastic leukemia at diagnosis and during treatment by single-cell DNA amplicon sequencing

  Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations and deletions, which are often associated with additional single nucleotide mutations. In this study we used single-cell targeted DNA sequencing to determine the clonal heterogeneity of B-cell ALL at diagnosis and during chemotherapy treatment. With a customly designed DNA amplicon library targeting the most common mutations (in 110 genes) present in ALL, we analyzed bone marrow samples and/or blood samples from 12 B-ALL cases at diagnosis. For 4 cases where we detected multiple mutational clones at diagnosis, we also studied blood samples during the first weeks of chemotherapy treatment. This study shows that B-ALL cases with either a ETV6-RUNX1 or a BCR-ABL1 fusion have a low mutational burden, while cases with PAX5 alterations or hyperdyploidy have multiple clones at diagnosis, often with mutations in the JAK-STAT signaling pathway and the RAS signaling pathway. As expected, it can be observed that these clones disappear during treatment of the leukemia with almost no mutated cells left after two weeks of treatment.

  Study EGAS00001005029

• Genomic and Transcriptomic Profiling of Patients with Malignant Pleural and Peritoneal Mesothelioma: The NCI Cohort

  Malignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. Better understanding of mesothelioma genomics and transcriptomics could advance novel therapies. We performed whole-exome sequencing (WXS) of germline and tumors of 122 patients, and RNA-sequencing (RNA-Seq) of tumor samples of 100 patients with pleural, peritoneal, and tunica-vaginalis mesothelioma.The biospecimens used in this study were collected as a part of the Mesothelioma Natural History Protocol (https://clinicaltrials.gov/ct2/show/NCT01950572), wherein, samples were collected from subjects with malignant mesothelioma as listed in the eligibility criteria below and written consent from each participant was obtained before sample acquisition.

  Study phs002207

• Clinical and biomarker dataset

  Clinical & biomarker data from IMagyn050: treatment arm, treatment approach, outcome of surgery, ECOG PS, PD-L1 status, race, age, disease stage, progression free survival (investigator assessed), overall survival, histology, tumor mutation burden and status, genomic loss of heterozygosity, microsatellite status, BRCA1/2 mutation status, tissue of origin. Mutation status based on FoundationOne NGS for the following genes is also being provided: TP53, BRCA1, CCNE1, MYC, NF1, PIK3CA, RAD21, TERC, PRKCI, KRAS, RB1, BRCA2, ARID1A, AKT2, PTEN, KDM5A, NOTCH3, FGF12, ERBB2, CDK12, EMSY, WHSC1L1, BCL2L1, CDKN2A, GNAS, ARFRP1, ZNF217, SOX2, CCND2, FGF6, FGF23, LYN, MUTYH, AURKA, FGFR1, MCL1, MLL2, MYCL1, ZNF703, BRAF, MAP2K4, CREBBP, TSC2

  Dataset EGAD00001009797

• Next-Generation Sequencing of AV Nodal Reentry Tachycardia patients

  Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients below 40 years of age. Familial clustering, early onset of symptoms, and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System.In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes.This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.

  Study EGAS00001002745

• Final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial evaluating peri-operative atezolizumab for early-stage triple-negative breast cancer

  In IMpassion031, adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate (primary endpoint) for stage II/III triple-negative breast cancer (TNBC). Patients with stage II/III TNBC were randomized 1:1 to neoadjuvant chemotherapy plus peri-operative atezolizumab or pre-operative placebo. Descriptive secondary endpoints included event-free, disease-free, and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival HR 0.76, 95% CI: 0.47–1.21). Among patients without pCR, 14/70 (20%) atezolizumab-treated and 33/99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory analyses, pCR was prognostic for long-term outcome. Patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. Adding atezolizumab to chemotherapy for stage II/III TNBC is associated with more favorable long-term outcomes. ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935

  Study EGAS50000000974

• METABRIC miRNA landscape

  MicroRNAs (miRNAs) are key players in cancer pathogenesis1. They display differential expression across breast cancer subtypes, and play oncogenic and tumor-suppressive roles2-6. A systematic study of the global miRNA landscape in breast cancer and the factors shaping it has not been undertaken. Here we report the results of profiling miRNA expression in 1,302 breast tumors with detailed clinical annotation and long-term follow-up, and for which matching genomic and mRNA expression data were available7. This provides a comprehensive view of the quantity, distribution and variation of the miRNA population and dissects how much genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture. The key clinical parameters and cellular pathways related to the miRNA landscape are identified, exemplified by context-dependent interaction with cell adhesion and Wnt signaling. Strikingly, in breast cancer miRNAs appear to act as modulators of mRNA-mRNA interactions rather than molecular switches. We demonstrate an important modulatory role for miRNAs in the biology of breast tumors devoid of somatic copy number aberrations, a common subtype where immune response is prominent. Remarkably, prognostic miRNA signatures derived in this subtype are consistently prognostic across several other subtypes and validate in external cohorts. These findings represent a new framework to study the biology of miRNA in human cancer.

  Study EGAS00000000122

• Filtered variants including SLC12A2 in patients with hearing loss

  Hereditary hearing loss is challenging to diagnose because of the heterogeneity of the causative genes. Further, some genes involved in hereditary hearing loss have yet to be identified. Using whole-exome analysis of three families with congenital, severe-to-profound hearing loss, we identified a missense variant of SLC12A2 in five affected members of one family showing a dominant inheritance mode, along with de novo splice-site and missense variants of SLC12A2 in two sporadic cases, as promising candidates associated with hearing loss.

  Study JGAS000379

• RNA-seq data from hypothalamic tissue from individuals with Prader-Willi syndrome and age-matched controls.

  RNA-seq data (bam files) from the hypothalamus of 4 individuals with Prader-Willi syndrome and 4 age-matched control individuals. Detailed information about the study design, case-control matching and RNA-seq data processing is provided in the accompanying publication [Bochukova et al (2018) Cell Reports].

  Dataset EGAD00001004034

• LLDeep DAG2+: scRNA-seq in PBMCs

  Single cell transcriptomics of PBMCs of 47 donors from the Lifelines Deep cohort (general population, Northern part of the Netherlands). Cells of five or six different donors were pooled together in one sample pool, resulting in eight different sample pools. In total, 28.855 cells were captured and their transcriptomes were sequenced to an average depth of 74k. Genotype data was available for each donor, which allowed us to use the Demuxlet method that uses variable SNPs between the pooled individuals to determine which cell belongs to which individual. Since genotype information is lacking of 2 individuals, the transcriptome of only 45 individuals could be retrieved.

  Dataset EGAD00001003459

• Proteogenomics of chronic lymphocytic leukemia

  Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterized the proteome and transcriptome in-depth alongside genetic and ex-vivo drug response profiling in a clinically well annotated CLL discovery cohort (n= 68). Unsupervised clustering of the proteome data revealed six subgroups. Five of these proteomic groups were associated with genetic features, while one group was only detectable at the proteome level. This new group was characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). We developed classifiers to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n= 165, n= 169) and confirmed that ASB-CLL comprises about 20 % of CLL patients. The inferior overall survival observed in ASB-CLL was independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling. This is the transcriptomics data of the discovery cohort.

  Study EGAS00001005746

• Genetic heritage of the Baphuthi highlights an over-ethnicised notion of 'Bushman' in the Maloti-Drakensberg, southern Africa

  Using contemporary people as proxies for ancient communities is a contentious but necessary practice in anthropology. In southern Africa, the distinction between the Cape KhoeSan and eastern KhoeSan remains unclear as ethnicity labels have been changed through time and most communities were decimated if not extirpated. The eastern KhoeSan may have had genetic distinctions from neighbouring communities who speak Bantu languages and KhoeSan further away, alternatively the identity may not have been tied to any notion of biology, instead denoting communities with a nomadic 'lifeway' distinct from African agro-pastoralism. The Baphuthi of the 1800s in the Maloti-Drakensberg, southern Africa had a substantial KhoeSan constituency and a lifeway of nomadism, cattle raiding, and horticulture. Baphuthi heritage could provide insights into the history of the eastern KhoeSan. We examine genetic affinities of 23 Baphuthi to discern whether the narrative of KhoeSan descent reflects distinct genetic ancestry. Genome-wide SNP data (Illumina GSA) were merged with 52 global populations, for 160K SNPs. Genetic analyses show no support for a unique eastern KhoeSan ancestry distinct from other KhoeSan or southern Bantu-speakers. The Baphuthi have strong affinities with early-arriving southern Bantu-speaking (Nguni) communities, as the later-arriving non-Nguni show strong evidence of recent African admixture possibly related to Late-Iron Age migrations. The references to communities as 'San',and 'Bushman' in historic literature has often been misconstrued as notions of ethnic/biological distinctions. The terms may have reflected ambiguous references to non-sedentary polities instead, as seems to be the case for the eastern ‘Bushman’ heritage of the Baphuthi.

  Study EGAS00001007080

• MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

  Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.

  Study EGAS00001001199

• Genome-to-genome analysis highlights the impact of the human innate and adaptive immune systems on the hepatitis C virus

  Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. We use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control.

  Study EGAS00001002324

• Tobacco exposure and somatic mutations in normal human bronchial epithelium

  That tobacco smoking causes lung cancer is well-established, but we lack quantitative understanding of its effects on genomes of normal bronchial epithelium. We sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking is the major influence on mutation burden, adding 1000-10,000+ mutations/cell, massively increasing both between-subject and within-subject variance, and generating several distinct signatures of substitutions and indels. A population of cells in subjects with smoking history had mutation burdens equivalent to that expected for never-smokers: these cells lacked tobacco-specific mutational signatures, were four-fold more frequent in ex-smokers than current smokers, and had significantly longer telomeres than their more mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged never-smokers. In current smokers, ≥25% of cells carried driver mutations and 0-6% cells had 2 or even 3 drivers. Thus, tobacco smoking increases mutation burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.

  Dataset EGAD00001005193

• Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging

  In this study we characterised the consequences of DNMT3A- and TET2-mutations in human clonal haematopoiesis. We screened 195 bone marrow samples for mutations by targeted DNA sequencing, and sequenced 99 paired peripheral blood samples to compare mutation detection between bone marrow and blood. We performed single-cell analysis with TARGET-seq+ on 13 samples (4 controls and 9 clonal haematopoiesis samples), which combines single-cell genotyping for targeted mutations with whole transcriptome sequencing on FACS sorted cells. Single-cell genotyping and transcriptomes were sequenced separately and linked by common single-cell identifiers.

  Study EGAS00001007358

• A genome scan for genes underlying adult body size differences between Central African hunter-gatherers and farmers.

  The evolutionary and biological bases of the Central African pygmy phenotype, a characteristic of rainforest huntergatherers defined by reduced body size compared with neighboring farmers, remain largely unknown. Here, we perform a joint investigation in Central African hunter-gatherers and farmers of adult standing height, sitting height, leg length, and body mass index (BMI), considering 358 hunter-gatherers and 169 farmers with genotypes for 153,798 SNPs. In addition to reduced standing heights, hunter-gatherers have shorter sitting heights and leg lengths and higher sitting/standing height ratios than farmers and lower BMI for males. Standing height, sitting height, and leg length are strongly correlated with inferred levels of farmer genetic ancestry, whereas BMI is only weakly correlated, perhaps reflecting greater contributions of non-genetic factors to body weight than to height. Single- and multi-marker association tests identify one region and eight genes associated with hunter-gatherer/farmer status, and 24 genes associated with the height-related traits. Many of these genes have putative functions consistent with roles in determining their associated traits and the pygmy phenotype, and they include three associated with standing height in non-Africans (PRKG1, DSCAM, MAGI2). We find evidence that European height-associated SNPs or variants in linkage disequilibrium with them contribute to standing- and sitting-height determination in Central Africans, but not to the differential status of hunter-gatherers and farmers. These findings provide new insights into the biological basis of the pygmy phenotype, and they highlight the potential of cross-population studies for exploring the genetic basis of phenotypes that vary naturally across populations. Pemberton et al. Human Genetics 2018 https://doi.org/10.1007/s00439-018-1902-3

  Study EGAS00001002975

• MAITS in HCC

  Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death and can be considered a prototype of inflammation-derived cancer arising from chronic liver injury. The cell composition of the HCC tumor immune microenvironment (TiME) has a major impact on cancer biology as the TiME can have divergent capacities on tumor initiation, progress, and response to therapy. Recent development of multi-omics and single-cell technologies help us to comprehensively quantify the cellular heterogeneity and spatial organization of the TiME and to further our understanding of antitumor immunity. We investigated the cellular composition of liver cancer patient samples (n=8) using single-cell RNA-seq. For this purpose, mononuclear cells were isolated from human liver cancer samples. Three locations within the tumor-bearing liver were used: adjacent liver, rim and tumor core. Then, cells were FACS sorted (either CD45+ cells or MAIT cells) and subjected to 10X Chromium-based scRNA-seq. We investigated immune cell changes and the cellular heterogeneity of the HCC TiME with a focus on MAIT cells. Annotated H5 files are provided. Clinical metadata including TMN stage, sex, gender, ethnicity, pretreatment, and histopathological reports are available for all patient samples. Further details on the study can be obtained in our paper once it’s published.A complementary dataset derived from ultrahighplex CO-Detection by indEXing (CODEX) from paired patient samples can be accessed through The Cancer Imaging Archives (TCIA) under DOI: https://doi.org/10.7937/bh0r-y074.

  Study phs003279

• Single-cell RNA-sequencing of CD34+ bone marrow cells from patients with SLE, healthy individuals and umbilical cord blood samples

  All immune cells that contribute to the pathogenesis of systemic lupus erythematosus (SLE) derive from adult haematopoietic stem and progenitor cells (HSPCs) within the bone marrow (BM). We reasoned that the fundamental abnormalities in the disease can be traced back to HSPCs. The aim of this study was to delineate human haematopoietic CD34+ progenitor subpopulations and to identify deregulated pathways in each subpopulation in SLE as compared to healthy controls and umbilical cord blood samples. This study revealed both quantitative-as evidenced by decreased numbers of non-proliferating early progenitors and qualitative differences- characterized by an IFN signature, which is known to drive loss of function and depletion of HSPCs.

  Study EGAS00001007317

• Exome sequencing of Congenital Heart Disease families Royal Brompton

  This project aims to study at least 90 exomes from families with congenital heart disease. The samples have been selected at the Royal, Brompton Hospital in collaboration with Stuart Cook and Piers Daubeney. Ethic approval has been sought for in the UK and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and Atrioventricular Septal Defect (AVSD). The indexed Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).

  Dataset EGAD00001000797

• Ancestry and somatic profile predict acral melanoma origin and prognosis – WXS

  Acral melanoma, which is not ultraviolet (UV)-associated, is the most common type of melanoma in several low- and middle-income countries including Mexico. Latin American samples are significantly underrepresented in global cancer genomics studies, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures. To address this, we characterise the genome and transcriptome of 123 acral melanoma tumours from 92 Mexican patients, a population notable because of its genetic admixture. Compared with other studies of melanoma, we found fewer frequent mutations in classical driver genes such as BRAF, NRAS or NF1. While most patients had predominantly Amerindian genetic ancestry, those with higher European ancestry had increased frequency of BRAF mutations and a lower median number of structural variants. The tumours with activating BRAF mutations have a transcriptional profile more similar to cutaneous non-volar melanocytes, suggesting that acral melanomas in these patients may arise from a distinct cell of origin compared to other tumours arising in these locations. KIT mutations were found in a subset of these tumours, and quadruple wild-type samples (non BRAF/NRAS/NF1/KIT) differed from mutated samples in their structural genomic profile and overall and recurrence-free survival patterns. Transcriptional profiling defined three expression clusters; these characteristics were associated with recurrence-free and overall survival. We highlight potential novel low-frequency drivers, such as PTPRJ, NF2 and RDH5. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.

  Dataset EGAD00001015755

• Mitochondrial DNA sequencing in samples of Huntington’s disease patients

  Mitochondrial dysfunction is found in the brain and peripheral tissues of Huntington’s disease (HD) patients, which connects many pathological features of HD. In this project, we conducted a large-scale study of mtDNA variations with a sensitive mtDNA-targeted sequencing method called STAMP, at a median coverage of 4000-fold, in lymphoblast and blood samples of HD patients. mtDNA sequence variations and copy numbers were compared between samples from HD patients and healthy control individuals, and were assessed in relation to HD stages, and changes of HD phenotypes in longitudinal samples.

  Study EGAS00001004092