Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

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Rantala , J K , Edgren , H , Lehtinen , L , Wolf , M , Kleivi , K , Vollan , H K M , Aaltola , A-R , Laasola , P , Kilpinen , S , Saviranta , P , Iljin , K & Kallioniemi , O 2010 , ' Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2 ' , NeoPlasia , vol. 12 , no. 11 , pp. 877-888 . https://doi.org/10.1593/neo.10548

Title: Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2
Author: Rantala, Juha K.; Edgren, Henrik; Lehtinen, Laura; Wolf, Maija; Kleivi, Kristine; Vollan, Hans Kristian Moen; Aaltola, Anna-Riina; Laasola, Petra; Kilpinen, Sami; Saviranta, Petri; Iljin, Kristiina; Kallioniemi, Olli
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2010
Language: eng
Number of pages: 23
Belongs to series: NeoPlasia
ISSN: 1522-8002
URI: http://hdl.handle.net/10138/23873
Abstract: Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.
Subject: EUKARYOTIC DNA-REPLICATION
GENE-EXPRESSION PROFILES
EPITHELIAL-MESENCHYMAL TRANSITION
CHROMOSOMAL INSTABILITY
NEOPLASTIC TRANSFORMATION
MICROARRAY ANALYSIS
COLORECTAL-CANCER
MUTATION STATUS
COLON-CANCER
COMPLEX
312 Clinical medicine
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