Patients with metastatic urothelial carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001002114 | EGA |
REPOSITORIES: EGA
Publications
Spatial and temporal clonal evolution during development of metastatic urothelial carcinoma.
Thomsen Mathilde B H MB Nordentoft Iver I Lamy Philippe P Høyer Søren S Vang Søren S Hedegaard Jakob J Borre Michael M Jensen Jørgen B JB Ørntoft Torben F TF Dyrskjøt Lars L
Molecular oncology 20160817 9
Patients with metastatic bladder cancer have a median survival of only 13-14 months. Precision medicine using targeted therapy may improve survival. Here we investigated spatial and temporal tumour evolution and tumour heterogeneity in order to evaluate the potential use of targeted treatment of metastatic bladder cancer. We performed a proof-of-concept study by whole exome sequencing of multiple tumour regions (n = 22) from three patients with metastatic bladder cancer. DNA from primary and met ...[more]
Similar Datasets
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.
2010-12-01 | E-GEOD-20718 | biostudies-arrayexpress
Project description:The development of metastases is a complex multi-step process manifested by diverse patterns, involving single or multiple organs and different time-courses of distant recurrences. The aim of this study was to characterise molecular patterns associated with patterns of organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases. This study includes patients with four patterns of first metastatic sites: bone only (with no visceral metastases within 6 months of first metastasis); to viscera only (with no bone metastasis within 6 months of first metastasis); to bone and visceral organs within a 6 month period; and no recorded distant metastasis. The study population was composed of 5,061 patients diagnosed with invasive primary breast cancer without distant metastasis at the time of diagnosis between 1975 and 2005 from Guyâs Hospital. From the study population, an incidence-based case-control design was used to include patients from each of the metastatic groups and a control series randomly matched to cases according to having no reported metastasis up to the calendar date of metastasis. The aim of this expression profiling study was to characterise any molecular patterns that may be associated with the organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases.
2017-12-01 | E-MTAB-4003 | biostudies-arrayexpress
Project description:Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. The transcriptomic study comprises 16 samples from Lymph node metastasis from infiltrating ductal breast carcinoma, 18 samples from Primary node-positive infiltrating ductal,7 samples from Primary node-negative infiltrating ductal and 3 samples from Unaffected lymph node were included. Their RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.
2013-03-05 | E-GEOD-44408 | biostudies-arrayexpress
Project description:Gene expression profiling comparing biological mechanisms for lymphatic metastases in lung adenocarcinoma and squamous cell carcinoma Two-condition comparison: primary invasive tumors (TN+), without lymph node metastasis (TN-), matched tumor cells in metastatic lymph nodes (MT) in ADC and SCC separately
2011-08-30 | E-GEOD-29827 | biostudies-arrayexpress
Project description:Urothelial cancer cells UM-UC3 was orthotopically implanted in mouse bladder wall and then recycled for multiple cycles. Spontaneous tumor tissues including primaries, lymph node metastasis, distant metastasis (lung and bone) and circulating tumor cells (CTCs) were collected and the mRNA expression profiling was examed by microarray
2017-05-22 | GSE48496 | GEO
Project description: Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.
2013-03-05 | GSE44408 | GEO
Project description:This series represents 180 lymph-node negative relapse free patients and 106 lymph-node negate patients that developed a distant metastasis. Please see attached patient clinical parameters sheet for more information. Keywords: other
2005-02-23 | GSE2034 | GEO
Project description:By combining molecular pathology, mRNA profiling, and exome-sequencing we describe muscle-invasive bladder tumors and matched lymph-node metastases.
2018-08-20 | GSE101723 | GEO
Project description:Metastatic disease remains one of the most urgent clinical challenges accounting for over 90% of cancer-related deaths. Yet, the identification of novel therapeutic targets to fight or prevent metastatic disease has been hampered by the limited availability of clinically relevant mouse models of metastasis formation. To address this caveat, we developed a novel preclinical mouse model of spontaneous metastatic breast cancer that recapitulates the key biological events of the metastatic cascade and mimics the clinical course of metastatic disease in humans. Exploiting the conditional K14cre;CdhF/F;Trp53F/F mouse model of de novo mammary tumor formation, we orthotopically transplanted K14cre;CdhF/F;Trp53F/F derived mouse invasive lobular carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts. Once recipient mammary tumors were established, we mimicked the clinical setting and performed a mastectomy. Following surgery, recipient mice eventually succumbed to wide-spread clinically overt metastatic disease in lymph nodes, lungs and gastrointestinal tract. Using aCGH analyses, we explored the relationship between the genomic profiles of mammary donor tumors and paired recipient outgrowths and observed a strong correlation, indicating that the genomic profile of the parental K14cre;CdhF/F;Trp53F/F mILC is highly conserved in recipient mammary tumors. To investigate the genomic relationship between recipient mammary tumors and their metastases, we examined the correlation structure of genomic profiles derived from paired sets of primary tumors and metastases. Genomic profiles of clonally-related recipient mammary tumors were highly conserved in local and distant metastases, indicating that few genomic alterations occur during transition from a primary tumor to a distant site. To more thoroughly examine potential site-specific genomic alterations, we constructed so-called ‘delta-profiles’ by calculating the difference between the genomic profile of a recipient mammary tumor and its paired lymph node- and lung metastasis. Site-specific recurrent alterations were not observed in lymph node nor lung metastases. Taken together, these data show that genomic profiles of metastases are highly similar to those of parental recipient tumors and that, if changes occurred, they did not recur in different independent samples. We performed aCGH analyses on DNA isolated from K14cre;Cdh-/-;Trp53-/- derived donor mILCs (n=3) and their recipient mammary tumor outgrowths (n=10). Furthermore, we also analyzed genomic profiles derived from lung (n=10), tumor-draining (n=7) and distant lymph node metastases (n=5) isolated from the same recipient mice. DNA from each of these samples was hybridized against related donor splenic DNA.
2011-12-23 | E-GEOD-34666 | biostudies-arrayexpress
Project description:Metastasis is responsible for the majority of deaths in a variety of cancer types, including breast cancer. Although several factors or biomarkers have been identified to predict the outcome of patients with breast cancer, few studies have been conducted to identify metastasis-associated biomarkers. Quantitative iTRAQ proteomics analysis was used to detect differentially expressed proteins between lymph node metastases and their paired primary tumor tissues from 23 patients with metastatic breast cancer. Immunohistochemistry was performed to validate the expression of two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins in 190 paraffin-embedded tissue samples. These four proteins were further analyzed for their correlation with clinicopathological features in 190 breast cancer patients. We identified 637 differentially regulated proteins (397 upregulated and 240 downregulated) in lymph node metastases compared with their paired primary tumor tissues. Furthermore, bioinformatics analysis using GEO profiling confirmed the difference in the expression of EpCAM between metastases and primary tumors tissues. Two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins were associated with the progression of breast cancer. Obviously, EpCAM plays a role in the metastasis of breast cancer cells to the lymph node. We further identified αB-crystallin as an independent biomarker to predict lymph node metastasis and the outcome of breast cancer patients.
2019-08-29 | PXD013931 | Pride