8215 results for "canc*"

in 29.82 milliseconds.

• HCA_Female_Reproductive_Adult_WSSS_RNA

  HCA Endometrium_LM The endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women’s health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001004727

• Microbiota 16S sequencing study in NSCLC patients eligible for surgery without neoadjuvant treatment

  18 non-small cell lung cancer patients eligible for surgery without neaodjuvant treatment were included in the study at Centre Jean Perrin (France). Patients did not take any antibiotics, food supplements or immunostimulants 2 months prior to inclusion. During surgery, patients underwent partial or complete lobectomy where samples of non-malignant lung tissue, peritumoural tissue and tumour were resected from the removed lobe. This was preceeded by the washing of the removed lobe and obtaining the broncho-alveolar lavage fluid. These four sample types were analysed by 16S sequencing in 17 from 18 patients. The study is a part of the project "Characterization of Microbiota (Intestinal, From Lungs, and Upper Airways) in Patients With Non-small Cell Lung Carcinoma: Exploratory Study " which is registered under ref. NCT03068663 (clinicaltrials.gov).

  Study EGAS00001004728

• Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations

  Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.

  Study EGAS00001004752

• Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma

  PTEN is one of most frequently altered tumor suppressor genes in malignant tumors. The dominant negative effect of PTEN alteration suggests that aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hot-spot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that over-express these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties with regard to their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.

  Study EGAS00001004753

• Rucaparib in patients presenting a metastatic breast cancer with Homologous Recombination Deficiency, without germline BRCA1/2 mutation, pronostic value of high LOH genomic score and predictive value of HRDetect (microarray)

  Breast cancer may present genomic alterations leading to homologous recombination deficiency. PARP inhibitors have proved their efficacy in patients with HER2-negative metastatic breast cancer (mBC) harboring germline (g) BRCA1/2 mutations. We conducted the phase 2 RUBY trial to assess the efficacy of rucaparib in HER2-negative mBC with high genomic loss of heterozygosity (LOH) score or somatic, without gBRCA1/2 mutation. 220 of 711 patients with mBC screened for LOH presented high LOH score which was associated with a higher likelihood of death (HR = 1.39, 95% CI: 1.11-1.75, p = 0.005). The primary objective was not reached with a clinical benefit rate (objective response or SD>16 weeks) of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (14 and 32 months). HRDetect tended to be associated with response to rucaparib, whithout reaching statistical significance (median HRDetect responders versus non responders: 0.465 versus, 0.040, p = 0.2135). Our data suggests that a small subset of patients with high LOH score could derive benefit from PARP inhibitors.

  Study EGAS00001004755

• Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing

  Chromosomal translocations with immunoglobin (IG) loci are the classic drivers in a large subset of B-cell lymphomas. Detection of these translocations is important for confirmation of diagnosis and for prognosis and therapy decisions. Currently, molecular diagnosis of translocations in lymphomas is not addressed well by Next Generation Sequencing (NGS). The standard method for detection of translocations is Fluorescence In Situ Hybridization (FISH), which is labor-intensive, and can be difficult to interpret. There is a need for a robust technology that can be standardized. Targeted Locus Capture (TLC) selectively enriches and sequences entire genes based on the crosslinking of physically proximal sequences, and thereby enables complete sequencing of genes of interest, including detection of large structural variants. Because the technology is based on the crosslinking and fragmenting of DNA, it has particular advantages in the analysis of Formalin-Fixed, Paraffin-Embedded (FFPE) samples, in which DNA is inherently crosslinked and fragmented. In order to validate the FFPE-TLC technology as a novel approach for translocation detection in lymphoma samples, we have developed a panel assay containing genes with frequent translocations (MYC, BCL2, BCL6, IG loci). With this assay we have analyzed >140 lymphoma and control FFPE samples of variable input amounts and qualities that had previously been analyzed with FISH, and a subset also with standard targeted NGS. Good concordance with FISH results was observed for both translocation positive and negative samples. In 10 cases for which FFPE-TLC detected a relevant fusion and FISH had been called negative, discordance could be explained by higher sensitivity of FFPE-TLC or by inconclusive FISH results. In a specific case, FFPE-TLC detected a small-distance rearrangement on chromosome 3 that caused a BCL6 fusion but led to insufficient and therefore undetectable break-apart with FISH. Secondly, the FFPE-TLC approach was tested on a set of 19 B-cell lymphoma FFPE samples that had previously been analyzed using standard targeted NGS and FISH and was enriched for discordant results between these methods. FFPE-TLC-based NGS enables more robust translocation calling as the detection relies on broad sequencing coverage across the translocation partner rather than on breakpoint sequences only. In 3 cases, FFPE-TLC could proof false negative calls in standard targeted NGS due to breakpoints located in regions difficult to capture or to sequence. In 1 case, standard targeted NGS had made a false positive call on a breakpoint sequence that was shown to be caused by a small insertion rather than a genuine translocation. This study shows that FFPE-TLC promises to be a robust alternative for FISH analysis and standard targeted NGS procedures in lymphoma diagnostics and possibly in other cancers with frequent structural variants. The FFPE-TLC approach enables a single, DNA-based NGS test detecting both small mutations and translocations.

  Study EGAS00001004760

• Immunological hallmarks for clinical response to BCG in bladder cancer

  Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumour activity.

  Study EGAS00001004764

• Paediatric_CNS_tumour_autopsy_DNA

  Investigation of early embryonic mutations can reveal the earliest stages of normal tissue development and the origins of paediatric cancers. Through widespread sampling of tumour, adjacent normal and distant normal samples at autopsy and whole genome sequencing, we aim to establish the point at which lethal paediatic brain tumours diverge from normal development. With many such tumours associated with germline predisposition mutations, we will also be able to investigate the tissue-specific effects these mutations induce.

  Study EGAS00001004771

• ENCORE__New_Targets_for_Effective_Combination_Therapies_in_Tumors_with_Unmet_Medical_Need

  This study utilises 2G-CRISPR screens to identify effective target combinations in KRAS-mutant colorectal and triple-negative breast cancer cell lines.

  Study EGAS00001004775

• Genomics-based personalized oncology in cancer of unknown primary (CUP, project H021)

  To perform a comprehensive genomic characterization of 70 patients suffering from cancer of unknown primary (CUP) we used whole-exome, whole-genome, transcriptome and methylome analysis. We detected a substantial mutational heterogeneity with genes most commonly affected by SNVs, indels and fusions being TP53, TTN, MUC16, ABCA13, COL6A3, KRAS, LRP1B, XIRP2 and CSMD3. The most common fusion involved FGFR2, the most common focal deletion affected CDKN2A. A molecular tumor board recommended genomics-based therapies in 56/70 (80%) patients which were applied in 20/56 (35.7%) cases. Entity predictions based on transcriptome and methylome data could be made in up to 62/70 (88.6%) cases but were conclusive in only 16/48 (33.3%) cases. Germline analysis revealed 6 (likely) pathogenic mutations in 5 patients. Recommended therapies translated into a mean PFS2/1 ratio of 3.61 (median=2.25) with a median PFS1 of 89 days (n=17) compared to a median PFS2 of 182.5 days (n=20). Our data emphasize the clinical benefit of comprehensive genetic approaches in diagnostic and therapeutic management and underline the need for innovative, mechanism-based clinical trials in this heterogeneous group of diseases.

  Study EGAS00001004786

• RNA-seq study of a Princess Margaret Cancer Centre human acute myeloid leukemia patient cohort

  The PMCC AML RNAseq dataset consists of 81 AML patient samples (clinical data in Supplemental Table 11 of manuscript), processed in two batches. These patient samples are able to engraft in the NSG (NOD.Cg PrkdcscidIl2rgtm1Wjl /SzJ) mouse model. Five patients (90543, 598, 90240, 110484, 100500) were included in both batches. Viaably frozen material from the Leukemia Tissue Bank at Princess Margaret Cancer Centre/ University Health Network were thawed by dropwise addition of X-VIVO + 50% fetal calf serum supplemented with DNase (100μg/mL final concentration, Roche). RNA was extracted from bulk peripheral blood mononuclear cells (PBMC) using the RNeasy Micro Kit (Qiagen Inc.). A paired-end 76 base-pair flow-cell lane Illumina High seq 2000 yielded an average of 240 million sequence reads aligning to genome per sample at the Genome Sciences Centre, BC Cancer Agency for cohort 1. Cohort 2 was subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Centre for Applied Genomics, Sick Kids Hospital.

  Study EGAS00001004792

• BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

  Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.

  Study EGAS00001004809

• Comprehensive Genomic and Transcriptomic Analysis of Rare Cancers for Guiding of Therapy (H021)

  Here we analyzed the molecular profiles and clinical outcomes of 1,310 patients (proportion of rare cancers, 75%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. Based on 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved response and disease control rates (23.9% and 55.3%, respectively) compared to previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients.

  Study EGAS00001004813

• Transcriptional profiling of ovarian tumours and cell lines

  Purpose: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC. Experimental Design: ERV expression was assessed using EOC transcriptional data from TCGA and from an independent cohort (HH), as well as from untreated or DNMTi-treated EOC cell lines. LASSO logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells. Results: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+ T cells (r=0.46, p=0.0001). In vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of ERV expression by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells. Conclusions: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect anti-tumor immunity.

  Study EGAS00001004814

• Long-read and short-read isoform sequencing in breast cancer

  The goal of this project was to perform long-read RNA sequencing (LR-seq, PacBio) in combination with short-read RNA-seq for systematic characterization of the isoform diversity in primary breast tumor samples. We sequenced the full-length transcriptomes of 26 breast tumors and 4 normal breast samples.

  Study EGAS00001004819

• Alveolar Rhabdomyosarcoma case report

  Rhabdomyosarcoma (RMS) is a mesenchymal malignancy phenocopying muscle and is among the leading causes of death from childhood cancer. Metastatic alveolar rhabdomyosarcoma is the most aggressive subtype with an 8% five-year disease-free survival rate when a chromosomal fusion is present, and 40% five-year disease-free survival rate when negative for a fusion event. The underlying biology of PAX-fusion negative alveolar rhabdomyosarcoma remains largely unexplored and is exceedingly rare in Li-Fraumeni syndrome patients. Here, we present the case of an 11-year old male with fusion-negative alveolar rhabdomyosarcoma studied at end of life with a comprehensive functional genomics characterization, resulting in identification of potential therapeutic targets for broader investigation.

  Study EGAS00001004828

• scRNA-seq of HGSC tumor and ascites

  Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few notable exceptions, their identities remain largely unknown. We uncovered the immune regulatory metabolic states and metabolomes of sorted tumor and stromal, CD4+, and CD8+ cells from the tumor and ascites of patients with high-grade serous ovarian cancer (HGSC) using high-dimensional flow cytometry and metabolomics supplemented with single cell RNA sequencing. Flow cytometry revealed that tumor cells show a consistently greater uptake of glucose than T cells, but similar mitochondrial activity. Cells within the ascites and tumor had pervasive metabolite differences, with a striking enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared to ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the gene encoding the enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Treatment of T cells with MNA resulted in an increase in T cell-mediated secretion of the tumor promoting cytokine tumor necrosis factor alpha. Thus, the TME-derived metabolite MNA contributes to an alternative and non-cell autonomous mechanism of immune modulation of T cells in HGSC. Collectively, uncovering the tumor-T cell metabolome may reveal metabolic vulnerabilities that can be exploited using T cell-based immunotherapies to treat human cancer.

  Study EGAS00001004829

• Effect_of_FAM50_knockout_on_the_transcriptome

  A knockout clone has been generated for both FAM50A and FAM50B; knockout of the other gene is then performed and the transcriptome is analysed to look at the effect of dual gene loss.

  Study EGAS00001004836

• Immune trajectory of response and adverse effect in immunotherapy-treated hepatocellular carcinoma

  Whilst anti-PD1 immune checkpoint blockade (ICB) has revolutionised treatment for many cancers, its response rates in hepatocellular carcinoma (HCC) remain modest, coupled with common incidences of immune-related adverse events (irAEs). To identify biomarkers and decipher the mechanisms for response and irAEs, we performed multi-dimensional immunoprofiling on peripheral blood and tissue collected before and during anti-PD1 ICB treatment from HCC patients. Single-cell analyses enabled us to identify peripheral biomarkers, in particular, CD11c+ antigen-presenting cells with varying degrees of HLA-DR expression and CD8 effector memory (EM) T cells with CXCR3 tissue-homing capability that are associated with both response and irAEs. We also dissected the mechanisms behind how these immune subsets interface between response and toxicity, showing their intersecting yet diverging trajectories leading to these distinct clinical fates. This study offers new insights on the mechanisms and potentially novel strategies to enhance response and ameliorate irAEs in cancer immunotherapy.

  Study EGAS00001004843

• Circulating Tumor DNA in Checkpoint Inhibitor treated Lung Cancer

  BackgroundImmune checkpoint inhibitors (ICI) are increasingly used to treat non-small cell lung cancer (NSCLC) and there is a critical need for novel predictive/prognostic biomarkers. We evaluated whether dynamics of circulating tumor (ctDNA) can identify NSCLC patients who benefit from single agent ICI.MethodsCirculating cell-free DNA (cfDNA) from 177 patients was analyzed prior ICI and at first treatment evaluation using a Commercial 77-gene panel. We performed de novo mutation calling and corrected for variants related clonal hematopoiesis. ctDNA changes were evaluated as predictors of tumor response estimated with PET/diagnostic CT and survival.ResultsMutations were detected in 159 of 174 (91.4%) analyzable patients. Most responders presented decreasing ctDNA levels, while non-responders had mixed molecular responses. Patients with a >50% molecular ctDNA decrease or no detectable ctDNA demonstrated improved PFS (5.9 versus 1.8 months; HR 0.49, 95%CI, 0.35-0.67, P < .001), and OS (18.9 versus 9.9 months; HR 0.41, 95%CI, 0.30-0.57, P < .001) compared to patients not achieving these endpoints. Clearance of mutations (and no detected ctDNA) had a similar effect (PFS HR 0.45, 95%CI, 0.32-0.61, P < .001; OS 0.37,95%CI, 0.27-0.52, P < .001) compared to patients having stable or additional mutations. After adjusting for clinical factors both >50% ctDNA decrease (HR 0.4, 95% CI, 0.3-0.6, P < .001) and clearance of mutations (HR 0.42, 95% CI, 0.3-0.6, P < .001) remained independent predictors for PFS and OS.ConclusionsctDNA testing reveals significant prognostic albeit not predictive information in ICI treated advanced NSCLC. This relevant information can be obtained with a commercial easy-to-implement ctDNA test that will facilitate extensive testing.

  Study EGAS00001004847

• Tumor HTG EdgeSeq from metastatic castrate resistant prostate cancer

  This dataset contains tumor bulk HTG EdgeSeq from patients with metastatic castrate resistant prostate cancer. RNA libraries were prepared following manufacturer's user guide (HTG Molecular Diagnostics). Each library was sequenced in HTG EdgeSeq system.

  Study EGAS00001004852

• Comprehensive genomic and transcriptomic analysis of three synchronous primary tumours and a recurrence from a head and neck cancer patient

  Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma patients. Here, we analysed three synchronous primaries and a recurrence from one patient, by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants which might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. Mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.

  Study EGAS00001004857

• Bulk-RNA Sequencing of high-grade pancreatic and non-pancreatic Neuroendocrine Neoplasms

  Therapeutic decisions in oncology depend on a precise pathological classification of individual neoplasms. Recent years have seen an intensification of research activities aimed at the extraction of clinically relevant information from patient-derived 'omics' data based on Machine-Learning models. However, a comprehensive training of Machine-Learning models requires sufficiently large numbers of training samples, which are usually not available for rare cancer types. The problem is worsened when individual tissues segregate into different cancer subtypes, as their discrimination would require even more training samples. Methods: Here, we report on a new data-augmentation technique to support the training of Machine-Learning models on ‘omics’ data from pancreatic neuroendocrine neoplasms (panNEN). PanNENs display all properties described above: Only about 2-3% of all pancreatic neoplasms are neuroendocrine and they fall into different subtypes with distinctly different prognosis, which makes the precise classification of such samples both difficult and important for therapy decisions. The approach reconstructs a given transcriptome based on healthy pancreatic cell type signatures and creates a Machine-Learning model that integrates the observed reconstruction error and predicted cell type proportions as features. Results: A benchmark of the deconvolution model predictions with the ground-truth found that the model could efficiently predict the sample grading, disease-related patient survival time, and differentiate between different subtypes in four panNEN and one mixed panNEN and non-pancreatic NENs dataset. We compared the predictive performance of the deconvolution-trained model to that of a model trained directly on the transcriptomic data, under inclusion of the Ki-67 classification gold standard biomarker, and found the performances to be comparable. Conclusion: Our approach serves as a data-augmentation technique to facilitate the training of Machine Learning models for rare cancer types via utilization of data from healthy origin. Additionally, the deconvolution results were clinically interpretable and further research can render the deconvolution approach an effective complementary asset for the clinical classification of neoplasms.

  Study EGAS00001004861

• 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

• Genetic makeup of agnospheres

  Agnospheres are cultures of cancer stem cells isolated from tissue biopsies from patients with Cancer of Unknown Primary (CUPs). The latter is a lethal malignancy (median survival <1 year), representing approximately the 3% of all cancers, and characterized by metastatic dissemination in the absence of a primary tumor recognizable by a standardized protocol including thorough body imaging and histopathological analysis. Agnospheres are long-term propagated in culture and, after subcutaneous injection into immunocompromised mice, they display high tumorigenicity and quickly reproduce the clinical presentation of the original tumor, featuring a multi-organ metastatic pattern and poorly differentiated histology. The goal of the project is to analyse the mutational profile of agnospheres in detail, as to verify its correspondance with that of the original tumors. Genetic information will be exploited to investigate the genetic drivers of the CUP phenotype, in particular the hypermetastatic ability and the differentiative block.

  Study EGAS00001004868