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Expression analysis of cancer of unknown primary (CUP)

ABSTRACT: Expression analysis of cancer of unknown primary (CUP)

PROVIDER: PRJNA517939 | ENA |

REPOSITORIES: ENA

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Expression analysis of cancer of unknown primary (CUP) 2

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Expression analysis of cancer of unknown primary (CUP) 2

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Expression analysis of cancer of unknown primary (CUP)

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Cancers of unknown primary (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin.

Project description:Employing genome wide transcriptome analysis,Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we created a successful classification model to identify the putative origin of a CUP. Using the classifications of the CUPs enable the comparison of transcriptome profiles from CUPs to the equivalent normal metastasis across the different carcinoma types. Gene Set Enrichment Analysis (GSEA) and Pathway analysis were used to reveal the common biological features characterizing CUPs. The classifier was build using 2208 samples of normal tissue, known primary tumors, metastasis of known origin and tested on 60 CUP samples. 130 of these samples were collected and analyzed as part of the project and submitted to ArrayExpress. The analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and by employing signatures of chromosome instability (CIN), we found that CUPs are chromosome unstable compared to metastases of known origin.

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Transcription profiling by array of human carcinomas of unknown primary

Project description:Carcinomas of unknown primary (CUP) are characterized by early metastatic dissemination in the absence of a detectable primary tumor. This disease accounts for about 3% of all malignant tumors. Most CUPs are poorly responsive to chemotherapy and have a rapid fatal evolution. The biological mechanisms supporting metastatic growth in various sites combined with regression or absence of growth in the primary site are still poorly understood. The aim of this project was to investigate characteristics of gene expression profile specific of CUPs with special attention to genes overexpressed or silenced in CUPs but not in classical secondary metastases. Three series of experiments were performed in 2006 and 2007. In all experiments, the mRNA used as a reference was obtained from diploid untransformed human fibroblasts (MRC5). The CUP samples were 2 xenografted CUP tumors (Capi1 and Capi3) and 4 CUP biopsies including a squamous carcinoma (Aud) and 3 adenocarcinomas (Gal, Pro, Gag). Samples representative of secondary metastases were xenografted tumors derived from metastases of nasopharyngeal carcinoma (C17), lung adenocarcinoma (IC14) and pancreatic adenocarcinoma (xenografted Capan 1 cell line) and one biopsy from a breast carcinoma (Vuc).

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