Transcriptome analysis of Follicular Lymphomas from the PRIMABIO cohort
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE93261 | GEO | 2018/02/19
REPOSITORIES: GEO
Similar Datasets
Project description:In neuroblastoma (NB), the presence of segmental chromosome alterations (SCA) is associated with a higher risk of relapse, even when occurring together with numerical chromosome alterations (NCA). Furthermore, recent evidence shows that SCAs play a role in tumor progression. In order to analyze the role of SCAs in infants with NB, we have performed an extensive retrospective array-CGH analysis of tumours from infants enrolled in the European INES 99.1, 99.2 and 99.3 trials. Tumour samples from 221/300 enrolled patients could be analyzed. SCAs were observed in 11%, 20% and 59% of infants enrolled in trial 99.1 (localised unresectable NB), 99.2 (INSS stage 4s) and 99.3 (INSS stage 4), respectively (p<0.001), and were associated with the presence of bone metastasis (p<0.003). Progression-free survival was poorer in patients whose tumours harbored at least one SCA, in the whole population as well as in trials 99.1 and 99.2. In multivariate analysis, taking into account single genetic alterations, the protocol arm and genomic profile, the SCA genomic profile was the strongest predictor of poor outcome. Although overall survival was excellent, patients with stage 4s disease and a SCA genomic profile had a higher risk of relapse also in the absence of clinical symptoms at diagnosis and required a higher treatment burden for salvage. In conclusion, in infants with NB, a SCA genomic profile is useful to identify patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas an NCA genomic profile can identify a patient subpopulation in whom treatment reduction can be considered safe. Each of the 218 tumoral genomic DNAs was hybridized against non-tumoral DNA reference on BAC/PAC array or commercial supports in order to determine an overall genomic profile. The reference DNA was obtained from the blood of a single normal individual.
2011-12-07 | E-GEOD-26494 | biostudies-arrayexpress
Project description:We evaluated whether targeted next-generation sequencing (NGS) using the Ion Torrent Personal Genome Sequencer of cfDNA could identify prognostic or predictive factors for overall survival (OS) or progression free survival (PFS) within a large cohort of patients with advanced lung adenocarcinoma enrolled in the GALAXY-1 trial.
2018-01-10 | E-MTAB-5749 | biostudies-arrayexpress
Project description:Background. 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. 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.
2014-09-03 | E-GEOD-56701 | biostudies-arrayexpress
Project description:In neuroblastoma (NB), the presence of segmental chromosome alterations (SCA) is associated with a higher risk of relapse, even when occurring together with numerical chromosome alterations (NCA). Furthermore, recent evidence shows that SCAs play a role in tumor progression. In order to analyze the role of SCAs in infants with NB, we have performed an extensive retrospective array-CGH analysis of tumours from infants enrolled in the European INES 99.1, 99.2 and 99.3 trials. Tumour samples from 221/300 enrolled patients could be analyzed. SCAs were observed in 11%, 20% and 59% of infants enrolled in trial 99.1 (localised unresectable NB), 99.2 (INSS stage 4s) and 99.3 (INSS stage 4), respectively (p<0.001), and were associated with the presence of bone metastasis (p<0.003). Progression-free survival was poorer in patients whose tumours harbored at least one SCA, in the whole population as well as in trials 99.1 and 99.2. In multivariate analysis, taking into account single genetic alterations, the protocol arm and genomic profile, the SCA genomic profile was the strongest predictor of poor outcome. Although overall survival was excellent, patients with stage 4s disease and a SCA genomic profile had a higher risk of relapse also in the absence of clinical symptoms at diagnosis and required a higher treatment burden for salvage. In conclusion, in infants with NB, a SCA genomic profile is useful to identify patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas an NCA genomic profile can identify a patient subpopulation in whom treatment reduction can be considered safe.
2011-12-07 | GSE26494 | GEO
Project description:Abstract from the associated publication: Although PET allows an accurate staging of disease in follicular lymphoma (FL) patients, the impact of pre-treatment maximum standardized uptake (SUVmax) value in this population remains elusive as well as its real biological significance. A training cohort of 48 FL patients and a validation cohort of 84 patients unpreviously treated were included retrospectively. SUVmax of 18-FDG PET was evaluated by centrally expert review and the optimum threshold of SUVmax value was determined in the training cohort to predict progression free survival (PFS). To explore the biologic meaning of PET results, tumor samples were analyzed from the two cohorts independantly :- the tumor microenvironment immune cartography by immunochemistry , - the cell gene-expression profiles assessed using Sample enrichment score combined to CIBERSORT method and - the tumor cell mutational profile determined by targeted Next Generation Sequencing (t-NGS). At baseline, patients with a SUVmax >14.5 had a significantly lower PFS compared to patients with SUVmax ≤14.5 (2y PFS: 40% vs 86%, HR = 0.16, p = 0.0009). The prognostic value of SUVmax was confirmed in the validation cohort (p= 0.006). Neither immune cell infiltration nor immune checkpoint expression were related to the baseline PET metrics including SUVmax. By constrast, high tumor cell proliferation (assessed by Ki67 staining) was significantly related to high SUVmax level ( p= 0.007). Interestingly FOXO1 mutated patients harbored high SUVmax and high tumor proliferation, that is why FOXO1 status could reflect to proliferation of FL tumor cells through SUVmax and Ki67 staining. So, FL patients with high baseline SUVmax related to high tumor cell proliferation have a poorer PFS despite absence of lymphoma transformation.
2020-12-31 | GSE148070 | GEO
Project description:Background. 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.
2014-09-03 | GSE56701 | GEO
Project description:Importance: Autophagy has been identified as a resistance mechanism to BRAF and MEK inhibition in BRAF mutant melanoma. In the BAMM trial, hydroxychloroquine (HCQ) was used to inhibit autophagy in combination with dabrafenib and trametenib in BRAF mutant melanoma patients. Objective: To a) determine safety and maximal tolerated dose (MTD) of hydroxychloroquine when combined with dabrafenib and trametinib and b) determine antitumor activity of the combination. Design: Open label non-randomized phase I/II clinical trial Setting: Prospective therapeutic clinical trial conducted in 4 centers Participants: Unresectable Stage III or Stage IV BRAF mutant melanoma patients Intrevention: HCQ twice daily, dabrafenib 150 mg twice daily and trametinib 2 mg daily (D+T) Main Outcome: Primary outcomes were safety and 1-year progression-free survival (PFS) rate Results: Between December 2014 and January 2020, 50 patients were screened, 38 patients were enrolled and evaluable for toxicity and 34 patients were evaluable for 1-year PFS rate. Patient demographics were: 29% were ECOG PS 1, 47% had elevated LDH, 52% were Stage IV M1c or M1d and 53% had previously received therapy for advanced melanoma. In the phase I trial there was no dose limiting toxicity of HCQ at either 400 (n=3) or 600 (MTD) mg po bid combined with D+T. For the entire study population, the 1-year PFS rate was 41% (95% CI = ), median PFS was 11.9 months (95% CI = ), overall response rate (ORR) was 85% (95% exact CI=64-95%)and complete response rate of 41% (95% exact CI=25-59%). In a prespecificed subgroup analysis in 18 patients with elevated LDH, the ORR was 88% and median PFS was 8 months Conlusion and Relevance: The combination of HCQ, dabrafenib and trametinib was well tolerated and produced a high response rate but did not meet the prespecified criteria for success with respect to the 1-year PFS rate. In patients with elevated LDH , the response rate and PFS were encouraging. A randomized placebo controlled trial of dabrafenib and trametinib with/without HCQ in advanced BRAF mutant melanoma patients with elevated LDH and previously treated with immunotherapy is being conducted through the National Clinical Trial Network.
2022-01-07 | GSE193157 | GEO
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.
2012-02-09 | E-GEOD-32101 | biostudies-arrayexpress
Project description:KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Novel predictive markers are required to further improve the selection of patients for this treatment. Here, we assessed the influence of modification of KRAS by gene copy number aberration (CNA) and microRNAs (miRNAs) in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab. Formalin-fixed paraffin-embedded primary tumour tissue was used from 34 mCRC patients in a phase III trial, who were selected based upon their good (n=17) or poor (n=17) progression-free survival (PFS) upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene copy number at the KRAS locus was assessed using high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR. Good response was associated with 12p12.1 copy number loss, even in patients with a KRAS mutation, while copy number gain in wild-type KRAS patients was correlated with a poor response. In KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good response. In wild-type KRAS patients, miRNA expression did not predict response in a multivariate model. Thus, assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of patients eligible for anti-EGFR therapy. Copy number detection was performed using NimbleScan and Nexus software Formalin-fixed paraffin-embedded primary tumour tissue was used from 34 metastisized colorectal cancer patients in a phase III trial (CKTO 2005-02; ClinTrials.gov NCT00208546) of the Dutch Colorectal Cancer Group (DCCG), who were selected based upon their good (n=17) or poor (n=17) progression-free survival (PFS) upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab.
2012-01-01 | E-GEOD-32048 | biostudies-arrayexpress
Project description:Evaluation of pretreatment gene expression profiling features in elderly CLL patients; correlation with clinical outcome Evaluation of pretreatment gene expression profiling features in elderly CLL patients enrolled in a clinical trial; correlation with clinical outcome
2012-12-01 | E-GEOD-35935 | biostudies-arrayexpress