Affymetrix data for training of Endopredict algorithm
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE26971 | GEO | 2011/10/11
SECONDARY ACCESSION(S): PRJNA135911
REPOSITORIES: GEO
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2011-10-10 | E-GEOD-26971 | biostudies-arrayexpress
Project description:These data, combined with other cohorts (GSE6532, GSE12093, and qRT-PCR based cohorts), was used to construct the EP algorithm, which predicts the likelihood of developing of a distant recurrence of early stage breast cancer under endocrine treatment. In addition, EPclin, a combination of the EP score, the nodal status and the tumor size, was constructed. All samples used for the development of the EP algorithm were taken from patients who received adjuvant tamoxifen only. Fresh-frozen tumours obtained from three centers were profiled on HG-U133A arrays. In brief, starting from 5 µg total RNA, labeled cRNA was prepared using the Roche Microarray cDNA Synthesis, Microarray RNA Target Synthesis (T7) and Microarray Target Purification Kit (Roche Applied Science, Mannheim, Germany), according to the manufacturer’s instructions. Raw .cel file data were processed by MAS 5.0 software (AFFYMETRIX, Santa Clara, CA). In the analysis settings, the global scaling procedure was chosen which multiplied the output signal intensities of each array to a mean target intensity of 500. We selected those samples from the GSE6532 and GSE12093 cohorts that we considered appropriate for our analyses (n=130 and n=130) and calculated MAS5 expression values from the corresponding .CEL-Files. One of the selection criteria was the GPL96 platform we also used for our measurements. GSE26971_GSE12093_dataset.txt.gz and GSE26971_GSE6532_dataset.txt.gz files contain data for both cohorts including the GSM numbers in row A and MAS5 expression data in the remaining rows. Processing of .CEL-files of these samples was exactly the same as the processing of the .CEL-files of our own samples: GPL96, MAS5, TGT 500.
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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.
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