Project description:We generated a blood-derived transcriptional signature that discriminates patients with lung cancer from non-affected smokers. When applied to blood samples from one of the largest prospective population-based cancer studies (the European Prospective Investigation into Cancer and Nutrition), this signature accurately predicted the occurrence of lung cancer in smokers within two years before the onset of clinical symptoms. Such a blood test could be used as a screening tool to enable early diagnosis of lung cancer at a curable stage. All samples were taken from smokers. EPIC cases were taken from the EPIC trial (a large prospective epidemiological trial in Europe, and are incident cases), Cosmos and BC cases are prevalent cases from a Cologne, Germany based epidemiological trial.
Project description:In the current study, we used exon arrays and clinical samples from a previous trial (SAKK 19/05) to investigate the expression variations at the exon-level of 3 genes potentially playing a key role in modulating treatment response (EGFR, KRAS, VEGFA). Exon-level biomarkers for the response to targeted therapy bevacizumab/erlotinib were identified in patients with metastatic non-small cell lung cancer Multicenter, prospective, open-label, single-arm, phase II trial.
Project description:This was a prospective clinical trial testing the ability of gene expression models of drug sensitivity that were developed in human and canine cell lines and applied to outcomes in dogs treated with adjuvant carboplatin and/or doxorubicin. Tumor samples were collected prospectively, and gene expression analysis was conducted using Affymetrix Canine Genome 2.0 Arrays.
Project description:We conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy. Patients accessible to tumor biopsy were prospectively enrolled at the Paoli-Calmettes Institute in the PERMED01 study (ClinicalTrials.gov, NCT02342158). Genomic profiling of frozen tissue was established by whole-genome array comparative genomic hybridization (aCGH)
Project description:Identification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial. Our data showed that strict quality criteria for RNA integrity assessment and well calibrated and standardized RT-qPCR allows multicentre analysis of genes transcripts with high accuracy in the clinical context. More stringent criteria are needed for transcriptome analysis for clinical applications.
Project description:Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers. To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression-based classification and established prognostic markers. Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4x44K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n=634) by Kaplan-Meier estimates and Cox regression analyses. Combination of gene expression-based classification and established prognostic markers improves risk estimation of LR/IR neuroblastoma patients. We propose to implement our revised treatment stratification system in a prospective clinical trial.
Project description:Background: The high incidence of recurrence and unpredictable clinical outcome for paediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. Gain of chromosome 1q has been reported as a frequent aberration and correlate of adverse outcome in ependymoma. We therefore evaluated a prognostic role for 1q25 gain across three age-defined European clinical trial cohorts of paediatric intracranial ependymoma. Methods: The frequency of 1q gain in paediatric ependymoma was assessed across 51 tumours (42 primary, 9 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was evaluated by interphase FISH (iFISH) across 189 primary intracranial ependymomas from children treated on the CCLG/SIOP CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT group, n = 64). Results were correlated with clinical, histological and survival data. Findings: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (3/9, 33 %). Gain of 1q25 was the strongest independent predictor of tumour progression in both CNS9204 (HR 3·36, p = 0·0009) and BBSFOP (HR 4·10, p = 0·0009) trial cohorts. In contrast, 1q25 gain was not prognostic for the older CNS9904/RT only group (PFS: p = 0·37, OS: p = 0·95). Clinical variables implicated in adverse outcome amongst cohorts included incomplete tumour resection and posterior fossa location. Interpretation: This is the first study to prospectively identify then validate a prognostic genomic marker for childhood ependymoma across independent prospective trial groups. 1q25 gain predicts progression in primary chemotherapy cohorts but not those treated by post-operative radiotherapy. We propose 1q25 gain is incorporated as an adverse marker into future European chemotherapeutic clinical trial design.
Project description:Expression profiling of whole blood cells isolated from patients piror to undergoing cardiac catheterization. PREDICT is a prospective, multi-center coronary catheter-lab trial being run in the US for the purpose of identifying biomarkers associated with coronary disease. A summary of the trial can be found at http://clinicaltrials.gov (identifier # NCT00500617).
Project description:Background: The high incidence of recurrence and unpredictable clinical outcome for paediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. Gain of chromosome 1q has been reported as a frequent aberration and correlate of adverse outcome in ependymoma. We therefore evaluated a prognostic role for 1q25 gain across three age-defined European clinical trial cohorts of paediatric intracranial ependymoma. Methods: The frequency of 1q gain in paediatric ependymoma was assessed across 51 tumours (42 primary, 9 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was evaluated by interphase FISH (iFISH) across 189 primary intracranial ependymomas from children treated on the CCLG/SIOP CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT group, n = 64). Results were correlated with clinical, histological and survival data. Findings: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (3/9, 33 %). Gain of 1q25 was the strongest independent predictor of tumour progression in both CNS9204 (HR 3·36, p = 0·0009) and BBSFOP (HR 4·10, p = 0·0009) trial cohorts. In contrast, 1q25 gain was not prognostic for the older CNS9904/RT only group (PFS: p = 0·37, OS: p = 0·95). Clinical variables implicated in adverse outcome amongst cohorts included incomplete tumour resection and posterior fossa location. Interpretation: This is the first study to prospectively identify then validate a prognostic genomic marker for childhood ependymoma across independent prospective trial groups. 1q25 gain predicts progression in primary chemotherapy cohorts but not those treated by post-operative radiotherapy. We propose 1q25 gain is incorporated as an adverse marker into future European chemotherapeutic clinical trial design. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from flash frozen tumour specimens and patient-matched peripheral blood Copy number analysis of Affymetrix 500K SNP arrays was performed for DNA from 51 ependymomas and 40 constitutional DNA samples. Analysing broad genomic aberrations in 51 paediatric ependymomas, looking particularly at 1q gain.