Dataset Information

The acute effects of chemotherapy and radiotherapy on peripheral blood epigenetic age in early stage breast cancer patients

ABSTRACT: Genome wide DNA methylation profiling of human blood samples. The Illumina Infinium EPIC DNA methylation Beadchip was used to obtain DNA methylation profiles Survival has increased in early stage breast cancer (BC), and the late effects of cancer treatment can persist for decades. The molecular mechanisms underlying acceleration of age-related diseases after chemotherapy and radiotherapy are poorly understood. We examined epigenetic changes in peripheral blood in early stage BC patients undergoing either adjuvant radiotherapy, or adjuvant chemotherapy and radiotherapy. DNA methylation experiments were performed on peripheral blood samples from women collected prior to and following completion of adjuvant therapy. Methylation profiles were used to estimate three measures of epigenetic age acceleration - intrinsic, extrinsic, and phenotypic - as well as estimated cell counts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140038 | GEO | 2020/06/23

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

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.

Dataset Information

The acute effects of chemotherapy and radiotherapy on peripheral blood epigenetic age in early stage breast cancer patients

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure