Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis
| Autor: | Olivier Poch, Marc Guenneugues, Olivier Collignon, Dalia Lorphelin, Marie Brulliard, Frances T. Yen, Pierre Oudet, Pierre Vallois, Jean-Marie Monnez, Gilles Karcher, Benoit Thouvenot, O. Roitel, Virginie Ogier, Bernard Bihain, Emmanuel Gothié, Sandrine Jacquenet, Walter Lorphelin |
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| Přispěvatelé: | Institut Élie Cartan de Nancy (IECN), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), TOSCA, INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique (Inria), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Somatic cell
Single-nucleotide polymorphism Biology MESH: Base Sequence medicine.disease_cause MESH: Expressed Sequence Tags MESH: Variation (Genetics) Transcriptome 03 medical and health sciences 0302 clinical medicine Neoplasms Genetic variation medicine Humans Vimentin MESH: Neoplasms RNA Messenger Gene 030304 developmental biology MESH: RNA Messenger Genetics Expressed Sequence Tags 0303 health sciences Expressed sequence tag Multidisciplinary MESH: Humans Base Sequence Genetic Variation [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Biological Sciences Molecular biology Cell Transformation Neoplastic MESH: Cell Transformation Neoplastic 030220 oncology & carcinogenesis Cancer cell MESH: Vimentin Carcinogenesis |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2007, 104 (18), pp.7522-7. ⟨10.1073/pnas.0611076104⟩ Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (18), pp.7522-7. ⟨10.1073/pnas.0611076104⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0611076104⟩ |
| Popis: | Virtually all cancer biological attributes are heterogeneous. Because of this, it is currently difficult to reconcile results of cancer transcriptome and proteome experiments. It is also established that cancer somatic mutations arise at rates higher than suspected, but yet are insufficient to explain all cancer cell heterogeneity. We have analyzed sequence variations of 17 abundantly expressed genes in a large set of human ESTs originating from either normal or cancer samples. We show that cancer ESTs have greater variations than normal ESTs for >70% of the tested genes. These variations cannot be explained by known and putative SNPs. Furthermore, cancer EST variations were not random, but were determined by the composition of the substituted base (b0) as well as that of the bases located upstream (up to b − 4) and downstream (up to b + 3) of the substitution event. The replacement base was also not randomly selected but corresponded in most cases (73%) to a repetition of b − 1 or of b + 1. Base substitutions follow a specific pattern of affected bases: A and T substitutions were preferentially observed in cancer ESTs. In contrast, cancer somatic mutations [Sjoblom T, et al. (2006) Science 314:268–274] and SNPs identified in the genes of the current study occurred preferentially with C and G. On the basis of these observations, we developed a working hypothesis that cancer EST heterogeneity results primarily from increased transcription infidelity. |
| Databáze: | OpenAIRE |
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