Increasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor - the G-protein coupled receptor 5A (Gprc5a). We sought to understand the molecular consequences of Gprc5a loss and towards this we performed microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice to define a loss-of-Gprc5a gene signature. Moreover, we analyzed differential gene expression patterns between Gprc5a knockout normal lung epithelial cells as well as lung adenocarcinoma cells isolated and cultured from tumors of NNK-exposed Gprc5a knockout mice.
A Gprc5a tumor suppressor loss of expression signature is conserved, prevalent, and associated with survival in human lung adenocarcinomas.
Specimen part
View SamplesGenes differentially expressed among cells constituting an in vitro human lung carcinogenesis model consisting of normal, immortalized, transformed and tumorigenic bronchial epithelial cells were identified. The differentially expressed genes were then analyzed to determine their relevance to the gene expression patterns of clinical non-small cell lung cancer (NSCLC) samples as well as the clinical outcome of patients with this disease.
Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system.
Cell line
View SamplesNeuroendocrine prostate cancer (NEPC) is rare historically but may be increasingin prevalence as patients potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. Diagnosis can be straightforward when classic morphological features are accompanied by a prototypical immunohistochemistry profile, however there is increasing recognition of disease heterogeneity and hybrid phenotypes. In the primary setting, small cell prostatic carcinoma (SCPC) is frequently admixed with adenocarcinomas that may be clonally related, while a small fraction of SCPCs express markers typical of prostatic adenocarcinoma. Gene expression patterns may eventually help elucidate the biology underlying equivocal cases with discordant IHC, however studies to date have focused on prototypical cases and been based on few patients due to disease rarity.
Gene expression signatures of neuroendocrine prostate cancer and primary small cell prostatic carcinoma.
Subject
View SamplesWe sought to identify the carcinogenic mechanisms involved in RKO cell line with no evidence of activated -catenin/TCF regulated transcription, by comparison its gene expression profile to that of group of colorectal cancer cell lines selected to be mismatch repair
The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription.
Cell line
View SamplesBackground. Androgen receptor splice variant-7 (AR-V7) is a truncated form of the androgen receptor protein which lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of AR-V7 in circulating tumor cells (CTCs) from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone. Methods. We used quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) to interrogate CTCs for the presence or absence of AR-V7 from prospectively enrolled patients with metastatic castration-resistant prostate cancer initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status and PSA response rates, PSA-progression-free-survival (PSA-PFS), clinical/radiographic-progression-free-survival (PFS), and overall survival (OS). Multivariable Cox regression analyses were performed to determine the independent effect of AR-V7 status on clinical outcomes. Results. Thirty-one enzalutamide-treated patients and thirty-one abiraterone-treated patients were enrolled, of which 38.7% and 19.4% had detectable AR-V7 from CTCs, respectively. Among men receiving enzalutamide, AR-V7–positive patients had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median: 1.4 vs 6.0 months, P<0.001), PFS (median: 2.1 vs 6.1 months, P<0.001), and OS (median: 5.5 months vs not reached, P=0.002) compared to AR-V7–negative patients. Similarly, among men receiving abiraterone, AR-V7–positive patients had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median: 1.3 months vs not reached, P<0.001), PFS (median: 2.3 months vs not reached, P<0.001), and OS (median: 10.6 months vs not reached, P=0.006). The negative prognostic impact of AR-V7 was maintained after adjusting for full-length-AR expression. Conclusions. Detection of AR-V7 in CTCs from patients with castration-resistant prostate cancer is associated with resistance to enzalutamide and abiraterone. Overall design: A total of four metastatic castration-resistant prostate tumor samples from four patients were subjected to RNA-seq. Two samples were positive for androgen receptor splice variant 7 and the other two were negative for this variant.
AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
No sample metadata fields
View SamplesThe dataset consists of 266 NCCN very low/low or favorable-intermediate risk PCa patients who underwent diagnostic prostate biopsy between 2000 and 2014 and were treated with RP in six community or academic practices: University of Calgary, Cedars-Sinai, Spectrum Health, Cleveland Clinic, MD Anderson Cancer Center and Johns Hopkins. All patients had complete tumor pathology from biopsy and prostatectomy. Low risk PCa was defined as T1c or cT2a, and Gleason score (GS) 6, and PSA < 10ng/ml and favorable-intermediate risk was no greater than predominant GS 3 and percent positive biopsy cores < 50%, and either cT2b-cT2c or PSA 10-20ng/ml.
Validation of the Decipher Test for predicting adverse pathology in candidates for prostate cancer active surveillance.
Age, Specimen part
View SamplesRenal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.
BAP1 loss defines a new class of renal cell carcinoma.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesTranscriptom analysis of microdissect adrenal medulla after 8 weeks of cardiac pressure overload caused by transverse aortic constriction.
Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis.
Sex
View SamplesThese samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers.
Transcriptome instability as a molecular pan-cancer characteristic of carcinomas.
Specimen part
View SamplesThe highly conserved protein eIF5A found in archaea and all eucaryotes uniquely contains the posttranslationally formed amino acid hypusine. Despite being essential the functions of this protein and its modification remain unclear. To gain more insight into these functions temperature sensitive mutants of the human EIF5A1 were characterized in the yeast Saccharomyces cerevisiae.
Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the nonsense-mediated decay pathway.
No sample metadata fields
View Samples