Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

PKC isoforms - MDA-MB-231

ABSTRACT: PKCalpha, delta and epsilon were downregulated in MDA-MB-231 cells and mRNA expression was analyzed

ORGANISM(S): Homo sapiens

SUBMITTER: Christer Larsson

PROVIDER: E-MTAB-462 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Adaptable gene-specific dye bias correction for two-channel DNA microarrays.

Margaritis Thanasis T Lijnzaad Philip P van Leenen Dik D Bouwmeester Diane D Kemmeren Patrick P van Hooff Sander R SR Holstege Frank C P FC

Molecular systems biology 20090428

DNA microarray technology is a powerful tool for monitoring gene expression or for finding the location of DNA-bound proteins. DNA microarrays can suffer from gene-specific dye bias (GSDB), causing some probes to be affected more by the dye than by the sample. This results in large measurement errors, which vary considerably for different probes and also across different hybridizations. GSDB is not corrected by conventional normalization and has been difficult to address systematically because o ...[more]

PMID: 19401678

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Project description:High-grade serous ovarian cancer (HGSOC) exhibits significant genomic heterogeneity within a patient at presentation. Recent work has suggested that this heterogeneity is linked to the development of resistance and disease progression in that chemotherapy selects for minor resistant subclones embodied in presentation disease leading to short progression-free survival and resistant relapse. Cell line models support this by showing that relapse is not an immediate descendant of presentation disease, but so far no immediate clinical evidence has been provided that convincingly demonstrates the origin of relapse. It is further still unclear what evolutionary processes shape the mutational landscape of HGSOC in vivo and to what extent the degree of genomic heterogeneity impacts a patient's clinical outcome. We address these questions by inferring evolutionary trees of metastatic disease from structural variations between 138 cancer samples obtained from 17 patients undergoing neoadjuvant chemotherapy for HGSOC. Using novel phylogenetic methods, we quantify genomic changes in the course of chemotherapy and the degree of clonal expansion and show that these indices determine patient outcome with high accuracy. We demonstrate that relapse is indeed a minor subclone of presentation disease by verifying that the focal NF1 deletion of a relapse case was already present at biopsy. By leveraging the information contained in the evolutionary trees, we unveil the etiology of genetic heterogeneity and the tumorigenic potential of HGSOC cell populations. This is the first comprehensive study showing the origin, strength and effect of genetic heterogeneity in HGSOC in a clinical setting. In addition to its immediate clinical significance, it strengthens previous statements that single sample biopsies are seemingly insufficient to predict disease progression and stresses the importance of establishing multiple sampling as a routine approach in the clinic. Clinical data and tissue samples were collected on the prospective CTCR-OV03 and CTCR-OV04 clinical studies designed to identify biomarkers of heterogeneity.

Dataset Information

PKC isoforms - MDA-MB-231

Publications

Adaptable gene-specific dye bias correction for two-channel DNA microarrays.

Similar Datasets

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