Molecular subtype classification of urothelial carcinoma in Lynch syndrome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA414169 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.
2019-01-01 | GSE104922 | GEO
Project description:MSI analysis of Lynch syndrome urothelial cancers
| PRJEB58093 | ENA
Project description:Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset.
| S-EPMC6068353 | biostudies-literature
Project description:Heredity is a major cause of ovarian cancer. Lynch syndrome is associated with 10-12% risk of ovarian cancer, diagnosis at young age and a predilection for endometrioid and clear cell tumors. Global gene expression profiling applied to 25 Lynch syndrome-associated and 42 sporadic ovarian cancers revealed 335 differentially expressed genes and involvement of the mTOR and the MAPK/ERK pathways. The clear cell tumors had distinct expression profiles with upregulation of HER2 and apoptosis signaling pathways. The distinct expression profiles provide clues relevant for hereditary tumorigenesis and may be relevant for therapeutic strategies and refined diagnostics in ovarian cancer linked to Lynch syndrome. Ovarian cancers linked to Lynch syndrome (n=25) were compared to a matched series of sporadic ovarian cancers (n=42), selected from a population-based consecutive series in which hereditary was excluded based on family history, normal MMR protein staining and lack of mutations in BRCA1 and BRCA2.
2013-10-14 | E-GEOD-37394 | biostudies-arrayexpress
Project description:mRNA expression from adenomas of patients with Lynch Syndrome and Familial Adenomatous Polyposis
2018-04-16 | GSE106500 | GEO
Project description:Heredity is a major cause of ovarian cancer. Lynch syndrome is associated with 10-12% risk of ovarian cancer, diagnosis at young age and a predilection for endometrioid and clear cell tumors. Global gene expression profiling applied to 25 Lynch syndrome-associated and 42 sporadic ovarian cancers revealed 335 differentially expressed genes and involvement of the mTOR and the MAPK/ERK pathways. The clear cell tumors had distinct expression profiles with upregulation of HER2 and apoptosis signaling pathways. The distinct expression profiles provide clues relevant for hereditary tumorigenesis and may be relevant for therapeutic strategies and refined diagnostics in ovarian cancer linked to Lynch syndrome.
2013-10-14 | GSE37394 | GEO
Project description:Colorectal carcinomas arising in the context of Lynch syndrome, the most common inherited cancer syndrome, typically show deficiency of the DNA MMR (mismatch repair) system. Lack of functional MMR leads to accumulation of frameshift mutations at micosatellites (microsatellite instability, MSI). High load of highly immunogenic tumor-specific frameshift neoantigens results in strong immune response against Lynch syndrome MSI cancers. Previous studies have shown systemic immune responses against frameshift neoantigens in Lynch syndrome carriers long before tumor manifestation. In the present study, we analyzed the immune profile of normal colorectal mucosa in Lynch syndrome carriers without current or previous cancer history and in Lynch syndrome colorectal cancer patients, as well as of Lynch syndrome colorectal carcinomas. The unsupervised cluster analysis of gene expression data revealed a sharp differentiation between normal mucosa from Lynch syndrome individuals with and without manifest cancer as well as between normal mucosa in general and Lynch syndrome cancer tissue. Deconvolution analysis for predicting the prevalence of immune cell population among the three groups revealed 10 out of 14 investigated populations to be significantly different between the three tissue types (FDR=10%). In contrast to normal mucosa samples, tumor tissue showed overrepresentation of immune-suppressive cell populations, such as regulatory T cells and neutrophils. Taken together with the quantitative T cell density analysis on the basis of immunohistochemical T cell stainings, our data show strong immune infiltration of the normal colorectal mucosa in Lynch syndrome individuals even in the absence of a manifest cancer.
2022-03-14 | GSE178516 | GEO
Project description:[original title] Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. In the present investigation we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1, in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data shows that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathological data it was possible to distinguish two molecular subtypes of Ta and T1 tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low (G1/G2) and high grade (G3) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathological grading. We also present a gene expression signature with independent prognostic impact on metastasis and disease specific survival. We conclude that the combination of molecular and histopathological classification systems may provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type.
2010-06-14 | GSE19915 | GEO
Project description:[original title] Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. In the present investigation we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1, in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data shows that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathological data it was possible to distinguish two molecular subtypes of Ta and T1 tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low (G1/G2) and high grade (G3) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathological grading. We also present a gene expression signature with independent prognostic impact on metastasis and disease specific survival. We conclude that the combination of molecular and histopathological classification systems may provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type. 144 bladder cancer tumor samples and 12 normal samples were analyzed on 2-color cDNA or oligo microarrays using the Stratagene Universal Human Reference RNA as the common reference sample. 24 samples are hybridized to both the cDNA and oligo platform and these were used for merging of data from the two different gene expression platforms into a single expression matrix and for subsequent evaluation steps. The merged gene expression matrix used for analyses is supplied as a supplementary file (at the foot of this record). 103 of the samples were also analyzed on a BAC array containing ~32 000 BAC clones. Arrays were produced at the Swegene Centre for Integrative Biology at Lund University (SCIBLU).
2010-06-14 | E-GEOD-19915 | biostudies-arrayexpress
Project description:Lynch syndrome and Familial colorectal cancer type X (FCCTX) are clinically diagnosed using the same criteria, but genomic differences exist between these two groups and the genomic profiles share similarities with their sporadic counterparts, mismatch repair (MMR) deficient and proficient tumors, respectively. Array-based comparative genomic hybridization was performed on 91 tumors, comprising 23 Lynch syndrome (AH), 23 FCCTX (AA), 23 sporadic MMR deficient (AM) and 22 sporadic MMR proficient tumors, in order to identify differences between Lynch syndrome and FCCTX.
2012-06-01 | E-GEOD-38405 | biostudies-arrayexpress