6134 results for "canc*"

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• Cancer immune control needs senescence induction by Stat1 dependent cell cycle regulator pathways in tumours

  Immune checkpoint bloackade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, we show that deletion of the senescence-inducing cell cycle regulators p16Ink4a/p19Arf (Cdkn2a) or p21Cip1 (Cdkn1a) in the tumour cells abrogated both, the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest those cancer cells that escape from eradication.

  Study EGAS00001004151

• Genetic insights into the biological mechanisms governing human ovarian ageing

  Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry. These common alleles influence clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. Identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increase fertility and extend reproductive life in mice. Causal inference analyses using the identified genetic variants indicates that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases risks of hormone-sensitive cancers. These findings provide insight into the mechanisms governing ovarian ageing, when they act across the life-course, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

  Study EGAS00001004947

• JAK and STAT alterations in CD30 positive LPD

  Study EGAS00001004181

• Targeted sequencing of breast cancers with germline BRCA1/2 mutations

  Breast cancer is the most prevalent cancer in women, where a germline predisposition plays a substantial role. However, the effects of pathogenic germline variants on accompanying breast cancers have not been fully characterized in terms of somatic alterations. We obtained tumor samples from 30 patients with pathogenic germline variants in BRCA2 (n = 25) and BRCA1 (n = 5), as well as an additional 30 patients without pathogenic germline mutations, in which somatic mutations in common breast cancer drivers and CNAs were analyzed using targeted panel sequencing.

  Study EGAS00001004182

• cfRRBS on cfDNA from pediatric cancer

  In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner.

  Study EGAS00001004194

• Association of DNA-methylation profiles with immune responses in breast cancer patients

  Study EGAS00001004211

• NanoSring of PBMC from bladder cancer and RCC patients

  PBMCs from patients were isolated using 50 mL Leucosep™ tubes (Greiner Bio-One International, Germany) and Ficoll-Paque™ PLUS (GE Healthcare, Sweden). Whole blood drawn into sodium heparin blood collection tubes were diluted 3x with phosphate-buffered saline (PBS) without calcium or magnesium (Lonza, Walkersville, MD). Diluted cell suspensions were carefully layered on Leucosep tubes and centrifuged for 15 minutes at 800 x g at room temperature (RT). Interphase containing PBMCs were harvested and washed with PBS and subsequently centrifuged for 10 minutes at 250 x g at RT before further processing.

  Study EGAS00001004229

• Whole exome sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer

  Study EGAS00001004231

• TP53 variant detection analysis in high grade serous epithelial ovarian cancer

  The aim of this study was to detect in the DNA purified from PAP test samples collected years before the diagnosis of high grade serous epithelial ovarian cancer the presence of the clonal pathogenic TP53 variant identified in the matched primary tumor biopsy. In this specific part of the study, we analyzed FFPE tumor samples to identify clonal pathogenic variants to be tested in matched PAP tests.

  Study EGAS00001004361

• Whole transcriptome sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer

  All mRNA sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).

  Study EGAS00001004232

• Whole-exome sequencing of ovarian clear cell carcinoma in clinical outliers

  Whole-exome sequencing dataset for the Australian Ovarian Cancer Study (AOCS) and The Jikei University School of Medicine (JIKEI) ovarian clear cell carcinoma (OCCC) clinical outliers project, representing 10 donors. Although OCCC are commonly resistant to platinum based chemotherapy, good clinical outcomes are observed in a subset of patients. Exome sequencing was performed in 10 patients who had either unusually long survival (N=5) or had a very short time to progression (N=5).

  Study EGAS00001004248

• hereditary BrEAst Case CONtrol study

  The BEACCON study aimed to address the lack of power of previous studies to identify novel BC predisposition genes by performing extensive sequencing in 12,000 women (11,511 analysed following exclusions) and further enhancing power by using an ‘extreme phenotype’ design with enrichment of familial non-BRCA1 and BRCA2 cases, compared with a control population of older women with ongoing confirmation of cancer-free status at June 2019. Three-quarters of the 1303 candidate genes screened were selected based on empiric evidence from local (69 multi-case BC families) or international whole exome sequencing studies, and the remainder were included to provide detailed coverage of functional pathways with established associations with BC

  Study EGAS00001005043

• Genetic characterization of a Unique Neuroendocrine Transdifferentiation Prostate Circulating Tumor Cell - Derived eXplant (CDX) Model

  Study EGAS00001004272

• OSCC WES + WGS Boot et al. 2020

  Study EGAS00001004376

• Neoadjuvant immunotherapy leads to pathological responses in MMR proficient and MMR deficient early stage colon cancers

  PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86–100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8–55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8+PD-1+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.

  Study EGAS00001004160

• Comprehensive molecular characterization of brainstem glioma

  Brainstem gliomas are the most devastating and lethal tumors. Survival rates are among the lowest in all cancers and options for intervention are likewise low. Due to anatomical delicacy of these areas, resection of tumors is particularly difficult and attempted resections have high perioperative mortality rates. Genomic and epigenetic studies often provide a gateway to functional studies of specific classifications of tumors that can lead to major breakthroughs in diagnosis and treatment options.

  Study EGAS00001004341

• The data access committee for Detecting Liver Cancer Using Cell-Free DNA Fragmentomes

  Dac EGAC00001003279

• Personalised Mapping of Tumour Development in Synchronous Colorectal Cancer Patients

  We performed an in-depth characterisation of 12 tumours from 3 syCRC patients by analysing histopathological, whole genome sequencing and RNA-sequencing data. We assessed the extent of genetic overlap between synchronous tumours and examined associations between clinicopathological information and the molecular, microbial and immune features of each tumour genome.

  Study EGAS00001004413

• Bone metastatic biopsies of breast cancer patients progressing on endocrine therapies.

  Study EGAS00001004268

• Epigenetic analyses of methylation and nucleosome occupancy in cell-free DNA (cfNOMe)

  Cell-free DNA (cfDNA) has become essential in cancer diagnostics and prenatal testing. We investigate enzymatic cytosine conversion for epigenetic analyses of cfDNA and find that it reliably measures cytosine methylation and nucleosome occupancy. Whereas previously, separate experiments had to be performed to study either epigenetic marking, this approach delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic profiling of cfDNA.

  Study EGAS00001004370

• Genomic study of an AT-AML

  Ataxia Telangiectasia (A-T) is caused by biallelic mutations in ATM and confers predisposition to cancer, with acute myeloid leukaemia (AML) being rarely observed. We investigated an AML arising in an A-T patient for secondary genetic events by performing whole exome sequencing of serial samples over the disease course. AML samples were compared to a reference "germline" sample from a much earlier time point. Goldgraben et al 2020, Pediatric Blood & Cancer

  Study EGAS00001004392

• STM4 - Mouliere et al, 2018. Enhanced detection of circulating tumor DNA by fragment size analysis

  Study EGAS00001004418

• Whole genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

  Glioblastoma (GBM) has one of the worst five-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions.

  Study EGAS00001004379

• Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing

  Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we present MitoSAlt, a computational method for accurate identification, quantification and visualization of mtDNA deletions and duplications from whole genome, whole exome or transcriptome sequencing data. MitoSAlt was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease further demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy. MitoSAlt paves the way for simple and reliable determination of mtDNA deletions and duplications across a wide range of relevant conditions and available sequencing datasets.  

  Study EGAS00001004380

• RP-1843 Arcagen - Gastrointestinal rare cancers (GI)

  Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting two datasets that contain NGS files from gastrointestinal rare cancers (n=119): - Dataset 1 (32 patients): Mesothelioma of the peritoneum (n=21) and Pseudomyxoma peritonei/mucinous adenocarcinoma of the appendix (n=11) - Dataset 2 (87 patients): Intra-hepatic cholangiocarcinoma (n=47), Extra-hepatic, cholangiocarcinoma (n=16), Not specified Cholangiocarcinoma (n=9), Small bowel adenocarcinoma (n=6) and other rare GI cancer (n=9)

  Study EGAS00001006299

• Subtype specific studies of breast cancer progression. Milan cohort.

  The aim of this study is to compare DCIS and IBC in a subtype stratified manner in several genomic levels (gene expression, copy number, methylation).The data in this archive is supplementary to previously published data.

  Study EGAS00001004390

• Detailed molecular and immune marker profiling of archival prostate cancer samples

  Study EGAS00001004396

• GBM stem cell lines and PRMT5 inhibitor

  Study EGAS00001004397

• Sensitive detection of tumor mutations from blood and its application to immunotherapy prognosis

  Cell-free DNA (cfDNA) is attractive for many applications, including cancer detection, locating, and monitoring. A fundamental task underlying these applications is the SNV calling from cfDNA, which, however, faces a new challenge, namely, the generally very low tumor content in cfDNA. Thus all existing callers fail to achieve satisfactory performance. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this important challenge. Furthermore, by leveraging cfDNA’s comprehensive coverage of clonal landscape, for the first time cfSNV can profile mutations even in subclones. In both simulated and real patient data, cfSNV vastly outperforms existing tools, showing tens of times increase in sensitivity in detecting mutations with low allele frequency while maintaining high precision. cfSNV can enhance the clinical utilities of cfDNA by dramatically reducing the required sequencing depth and therefore reduce the cost by magnitudes, and further make the Whole-Exome-Sequencing of cfDNA a viable option. As an example, we demonstrate that cfDNA-WES allows a new biomarker to effectively select patients for immunotherapy.

  Study EGAS00001004373

• Accelerated single cell seeding in relapsed multiple myeloma

  Study EGAS00001004404

• Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer

  Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary endpoint, decreased Ki67, occurs in 12% of TNBC. Multiple different approaches identify HR deficiency in the majority of TNBC, 69% with the mutational-signature-based HRDetect assay. Cancers with mutational signatures of HR deficiency have a functional defect in HR. Following rucaparib treatment there is no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identify activity of rucaparib in cancers with mutation-signatures of HR deficiency, with rucaparib inducing expression of interferon response genes in HR deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors.

  Study EGAS00001004405

• Activating AKT1 and PIK3CA mutations in metastatic castration-resistant prostate cancer

  Study EGAS00001004328

• Sequencing of an adolescent patient with germline RET mutant alveolar rhabdomyosarcoma

  An adolescent patient presented with an alveolar rhabdomyosarcoma made more unique by the presence of a germline RET mutation ordinarily associated with and a known driver of multiple endocrine neoplasia type 2A (MEN2A) cancer. To better understand the role of this germline RET mutation in the genetics and phenotypic response of this unique alveolar rhabdomyosarcoma, we performed DNA and RNA sequencing of the patients in addition to functional studies on patient-derived cultures and genetically similar similar cell models.

  Study EGAS00001004359

• Scottish High Grade Serous Ovarian Cancer

  Scottish HGSOC samples were collected via local Bioresource facilities at Edinburgh, Glasgow, Dundee and Aberdeen and stored in liquid Nitrogen until required. HGSOC patients were determined from pathology records and were included in the study where there was matched tumour and whole blood samples. On receipt of tumour material the tumour was processed as follows: firstly, the tumour sample was divided into two for DNA and RNA extraction. Slivers of tissue were cut from the front and rear faces of the DNA sample, then fixed in formalin and embedded in paraffin wax. Sections from the front and rear tissues from all samples were examined by H&E staining supplemented by WT1/p53 immunohistochemistry if required. Following pathology review, samples were only included if they met the following criteria: they were confirmed as HGSOC and there was greater than 40% tumour cellularity throughout the tumour, determined using the H&E sections. Somatic DNA was extracted using the Qiagen DNeasy Blood and tissue kit (cat no 69504). The tissue was initially homogenised using a Qiagen Bioruptor, followed by the manufacturers recommended protocol (including RNase digestion step). Germline DNA was extracted from 1-3ml whole blood using the Qiagen FlexiGene kit (cat no 51206) following the manufacturers recommended protocol. The resulting DNA underwent quality control as follows: firstly, A260 and A280nm were measured on a Denovix DS-11 Fx to qualitatively illustrate A260/280nm and A260/230nm ratios as surrogate measures of DNA purity. A260/280 had to be 1.8 or greater and A260/230 had to be 2.0 or greater. Then, DNA was quantified using LifeTechnologies Qubit dsDNA BR kit (cat no Q32850) and we required a minimum of 50ul at 25ng/ul for WGS. Thirdly, DNA was diluted to 25ng/ul and a representative sample was loaded onto a 0.8% TAE gel, ran at 100v for 60mins and then imaged using a BioRad ChemiDoc imaging system to visualise the DNA quality. Only when all 4 quality control requirements were satisfied was the DNA sequenced. The DNA was sequenced at the Glasgow Precision Oncology Laboratories.

  Study EGAS00001004410

• Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma

  Study EGAS00001004430

• FOXM1 is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer that is detectable using metabolic imaging (RNA-seq data)

  PIK3CA, encoding the PI3Kα isoform, is the most frequently mutated oncogene in estrogen receptor-positive breast cancer. Isoform-selective PI3K inhibitors are used clinically but intrinsic and acquired resistance limits their utility. Improved selection of patients that will benefit from these drugs requires novel predictive biomarkers. We show here that persistent FOXM1 expression following drug treatment is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer. Since the transcription factor drives expression of lactate dehydrogenase (LDH) but not hexokinase 2 (HK-II), changes in FOXM1 expression can be detected using magnetic resonance imaging of LDH-catalyzed hyperpolarized 13C label exchange between pyruvate and lactate but not by PET measurements of HK-II-mediated trapping of the glucose analog 2-deoxy-2-[18F]fluorodeoxyglucose.

  Study EGAS00001004452

• Evolutionary analysis of pancreatic neoplastic cysts through whole-exome and targeted sequencing

  Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyzed 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing.

  Study EGAS00001004473

• Single cell RNAseq of PBMC from bladder cancer patients

  Study EGAS00001004458

• Whole-exome sequencing and microRNA profiling predicted relapse risk of stage I lung adenocarcinomas

  Despite the advance in precision therapy, about 20% of stage I non-small cell lung cancer patients suffer a relapse after surgical resection. To develop molecular signatures for relapse prediction of stage I lung adenocarcinoma (LUAD), we conduct comprehensive analyses of multiplatform molecular profiling from 113 treatment-naïve stage I Taiwanese LUAD patients. We identify 16 nonsynonymous non-sporadic point mutations (NSPOPMs) harbored at EGFR, KRAS, TP53, CTNNB1 and 6 other genes, and find that the Non-EGFR NSPOPMs were associated with early relapse in a dose-dependent manner via variant allele fraction (VAF). We define a score, maxVAF, to aggregate the VAFs of these NSPOPMs by the maximum value. MicroRNA expression analysis shows a strong correlation between miR-31 and maxVAF. Combining maxVAF with miR-31 led to a powerful risk prediction for surgically resected stage I patients (hazard ratio = 8.65, P = 0.001). Our study opens up more options for precision management of stage I LUAD patients.

  Study EGAS00001004461

• Whole exome sequencing of long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer

  Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1-year of treatment or exceptional cases of complete response to trastuzumab for ≥ 10 years. Identification of the underlying genomic aberrations of “exceptional responders (ExRs)” compared to “rapid non-responders (NR)” increases our understanding of the mechanisms involved in MBC progression and identification of biomarkers of trastuzumab response and resistance. Whole exome sequencing was performed on six ExRs compared to five NR. The overall fraction of genome copy number alteration (CNA) burden was higher in NR patients (P=0.07), while more significantly pronounced in copy number gains (P=0.03) in NR compared to ExRs. Delineation of the distribution of CNA burden across the genome identified a greater degree of CNA burden in NR within chr8 (P=0.02) and in chr17 (P=0.06) and conferred a statistically significant benefit in overall survival.

  Study EGAS00001004486

• Intratumoural heterogeneity and immune modulation in lung adenocarcinoma of female smokers and never smokers

  Lung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.

  Study EGAS00001006331

• ctDNA monitoring using patient-specific sequencing and integration of variant reads - Lung cohort

  Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

  Study EGAS00001004447

• ctDNA monitoring using patient-specific sequencing and integration of variant reads - Breast cohort

  Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

  Study EGAS00001004446

• RNA-seq data from 121 tumor samples with muscle invasive bladder cancer.

  In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (< pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). RNA-seq was performed using the QuantSeq kit FWD HT kit (Lexogen) using 500 ng input RNA from 121 tumor samples. Data provided here consist of 780 fastq files for RNA-seq.

  Study EGAS00001004505

• WES data from 165 tumor/germline samples with muscle invasive bladder cancer.

  In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (< pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). WES was performed using DNA from 165 tumors (76x median coverage) and associated germline DNA (46x median coverage). Data provided here consist of 5,828 fastq files for WES.

  Study EGAS00001004507

• Mutational landscape of eccrine porocarcinoma (sweat gland tumour)

  Eccrine porocarcinoma (EP) is the most common form of sweat gland malignancy. The aetiology of EP is largely unknown. The current lack of data on somatic mutation patterns in EP hampers the development of effective therapies. We performed whole-exome sequencing in a well-characterized sample of 14 matched EP tumour/healthy surrounding tissue samples. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. The analyses revealed alterations in the cancer driver genes and in crucial oncogenic pathways.

  Study EGAS00001004632

• UROMOL 2020 - SNP data

  The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.

  Study EGAS00001004862

• Multi Omics of glioma in the the Chinese Glioma Genome Atlas (CGGA) project

  Study EGAS00001004729

• Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer (NABUCCO Cohorts 1 and 2)

  Study EGAS00001004521

• Discovery of cancer prognostic markers based on comparison of gene expression in colorectal cancer samples.

  Here, we analyse bulk mRNA-seq data derived from normal tissues adjacent to tumors (NATs) and tumour tissues of colorectal cancer (CRC), including 80 NAT samples and 80 tumour samples.

  Study EGAS00001005068