title: A gene expression and pre-mRNA splicing signature that marks the adenoma-adenocarcinoma progression in colorectal cancer.
abstract: It is widely accepted that most colorectal cancers (CRCs) arise from colorectal adenomas (CRAs), but transcriptomic data characterizing the progression from colorectal normal mucosa to adenoma, and then to adenocarcinoma are scarce. These transition steps were investigated using microarrays, both at the level of gene expression and alternative pre-mRNA splicing. Many genes and exons were abnormally expressed in CRAs, even more than in CRCs, as compared to normal mucosae. Known biological pathways involved in CRC were altered in CRA, but several new enriched pathways were also recognized, such as the complement and coagulation cascades. We also identified four intersectional transcriptional signatures that could distinguish CRAs from normal mucosae or CRCs, including a signature of 40 genes differentially deregulated in both CRA and CRC samples. A majority of these genes had been described in different cancers, including FBLN1 or INHBA, but only a few in CRC. Several of these changes were also observed at the protein level. In addition, 20% of these genes (i.e. CFH, CRYAB, DPT, FBLN1, ITIH5, NR3C2, SLIT3 and TIMP1) showed altered pre-mRNA splicing in CRAs. As a global variation occurring since the CRA stage, and maintained in CRC, the expression and splicing changes of this 40-gene set may mark the risk of cancer occurrence from analysis of CRA biopsies.
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France.
authors: Marine
authors: M
authors: Pesson
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France ; Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors: Alain
authors: A
authors: Volant
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France ; Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors: Arnaud
authors: A
authors: Uguen
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France.
authors: Kilian
authors: K
authors: Trillet
authors: GenoSplice technology, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, Centre Hayem, Paris, France.
authors: Pierre
authors: P
authors: De La Grange
authors: Plateforme de Génomique Santé, Laboratoire de Génomique Médicale, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6290, Institut de Génétique et Développement de Rennes, Unité Mixte de Services 3480 Biosit, Université de Rennes 1, Rennes, France.
authors: Marc
authors: M
authors: Aubry
authors: Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors: Mélanie
authors: M
authors: Daoulas
authors: Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors: Michel
authors: M
authors: Robaszkiewicz
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France ; Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors: Gérald
authors: G
authors: Le Gac
authors: Institut de Recherche contre le Cancer Nantes Atlantique, Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 892, Centre Paul Papin, Angers, France.
authors: Alain
authors: A
authors: Morel
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France.
authors: Brigitte
authors: B
authors: Simon
authors: Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1078, Université de Bretagne Occidentale, Structure Fédérative de Recherche ScInBioS, Faculté de Médecine, Brest, France ; Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors: Laurent
authors: L
authors: Corcos
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D001706:Biopsy; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012322:RNA Precursors