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Expression data for 52 microsatellite stable (MSS) primary tumors from patients with proximal colon cancer.

ABSTRACT: Samples were taken from surgically resected tumor specimens from patients with proximal colon cancer. The expression profiles were determined using the Affymetrix GeneChip Human Exon 1.0 ST Array version 2. APC gene mutation status was determined using Sanger sequencing. A classifier for APC mutation status was trained using these expression data. 52 microsatellite stable (MSS) proximal colon cancers samples were analyzed. 17 samples were APC wild-type and 35 had APC protein-truncating mutations.

ORGANISM(S): Homo sapiens

SUBMITTER: Oliver Sieber

PROVIDER: E-GEOD-63624 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer.

Jorissen Robert N RN Christie Michael M Mouradov Dmitri D Sakthianandeswaren Anuratha A Li Shan S Love Christopher C Xu Zheng-Zhou ZZ Molloy Peter L PL Jones Ian T IT McLaughlin Stephen S Ward Robyn L RL Hawkins Nicholas J NJ Ruszkiewicz Andrew R AR Moore James J Burgess Antony W AW Busam Dana D Zhao Qi Q Strausberg Robert L RL Lipton Lara L Desai Jayesh J Gibbs Peter P Sieber Oliver M OM

British journal of cancer 20150825 6

<h4>Background</h4>APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.<h4>Methods</h4>APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort.<h4>Results</h4>Wild-type APC microsatel ...[more]

PMID: 26305864

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Expression data for 52 microsatellite stable (MSS) primary tumors from patients with proximal colon cancer.

Project description:Samples were taken from surgically resected tumor specimens from patients with proximal colon cancer. The expression profiles were determined using the Affymetrix GeneChip Human Exon 1.0 ST Array version 2. APC gene mutation status was determined using Sanger sequencing. A classifier for APC mutation status was trained using these expression data.

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Project description:Canonical Wnt signalling regulates the self-renewal of most if not all stem cell systems. In the blood system, the role of Wnt signalling has been subject of much debate, with positive and negative roles of Wnt signalling proposed for hematopoietic stem cells (HSC). As we have shown previously, this controversy can be largely explained by the effects of different dosages of Wnt signalling. What remained unclear however, was why high Wnt signals would lead to loss of reconstituting capacity. To better understand this phenomenon, we have taken advantage of a series of hypomorphic mutant Apc alleles resulting in a broad range of Wnt dosages in HSCs, purified those HSCs and performed whole genome gene expression analyses. Gene expression profiling and functional studies show that HSCs with APC mutations lead to high Wnt levels , enhanced differentiation and diminished proliferation, but have no effect on apoptosis, collectively leading to loss of stemness. Thus, we provide mechanistic insight into the role of APC mutations and Wnt signalling in HSC biology. As Wnt signals are explored in various in vivo and ex vivo expansion protocols for HSCs, our findings also have clinical ramifications. To investigate the effects of Wnt signals in hematopoietic cells, mice carrying floxed Apc or hypomorphic Apc mutants were crossed, LSK cells were isolated and treated with Cre IRES GFP gamma-retrovirus ex vivo, GFP+ cells were sorted and RNA expression was determined.

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2014-09-08 | E-GEOD-48684 | biostudies-arrayexpress

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