Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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High-through put translational in vivo and ex vivo techniques for glioma molecular characterization and accurate classification, prognosis and treatment selection subset data from etumour consorteum Kal1

ABSTRACT: Tumour expression profiling was performed on resected brain tumour tissue following its histological categorisation. Classification of tumour type was carried out according to WHO criteria by a panel of independent pathologists across the etumour consorteum. This gave a high quality diagnostic evaluation, enabling stratification of patients by tumour type and grade. Sample quality was further assessed throughout sample processing allowing the use of minimum quality standards to be applied to all samples prior to profiling. This approach yielded high quality data that combined with diagnostic stratification enabled profiling by tumour type and grade, allowing the identification and investigation of gene signatures associated with these categories.

ORGANISM(S): Homo sapiens

SUBMITTER: Kenneth Laing

PROVIDER: E-MTAB-1852 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Lymph-node (LN) metastases predict for high recurrence rates in breast cancer patients. Eradication of micro-metastatic tumor cells is the primary goal of adjuvant systemic treatment. Decisions regarding systemic treatment depend largely on primary tumor characteristics rather than on characteristics of their LN metastases. However, it remains unclear to what extent LN metastases, having already metastasized locally, resemble their primary breast tumors and as such will be eradicated by the systemic therapy chosen. In this study we investigated the genetic differences between primary breast cancers and their paired LN metastases using array comparative genomic hybridization analyses on a high resolution 720K Nimblegen platform. Thus far, no metastasis-specific genomic aberrations have been identified. We hypothesized that this is due to low-resolution platforms and lack of stratification on breast cancer subtypes (specifically, triple-negative (TN) versus luminal). Furthermore, we speculated that as TN tumours are known to be more genetically unstable, their LN metastases would show an increase in random copy number aberrations (CNAs). Therefore, we studied 10 primary TN breast tumourM-bM-^@M-^SLN pairs and 10 luminal pairs and found that all LN metastases clustered nearest to their matched tumour except for two. These two were explained by poor hybridization quality and, interestingly, the presence of two histological components in one tumour. We found no significantly altered CNAs between pairs in the whole group, nor when subdivided over subtypes; neither did we find a CNA increase in LN metastases compared to primary tumours within the TN subgroup, suggesting most CNAs are functional and not random. Our findings suggest a strong clonal relationship between primary breast tumours and its LN metastases and support the use of the primary tumor characteristics to guide adjuvant systemic chemotherapy in breast cancer patients, since primary tumors and their subsequent LN metastases seem remarkably similar, at least prior to treatment. The experiment contains 20 paired primary breast cancer samples with their lymph node metastases, analysed on a 720 whole genome CGH array. Additionally, for one sample its two distinct histological subpopulations were analysed on the same platform.

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High-through put translational in vivo and ex vivo techniques for glioma molecular characterization and accurate classification, prognosis and treatment selection subset data from etumour consorteum Kal1

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