title: Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis.
abstract: 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.
authors: Institut National Polytechnique de Lorraine, Vandoeuvre-lès-Nancy, France.
authors: Marie
authors: M
authors: Brulliard
authors: Dalia
authors: D
authors: Lorphelin
authors: Olivier
authors: O
authors: Collignon
authors: Walter
authors: W
authors: Lorphelin
authors: Benoit
authors: B
authors: Thouvenot
authors: Emmanuel
authors: E
authors: Gothié
authors: Sandrine
authors: S
authors: Jacquenet
authors: Virginie
authors: V
authors: Ogier
authors: Olivier
authors: O
authors: Roitel
authors: Jean-Marie
authors: JM
authors: Monnez
authors: Pierre
authors: P
authors: Vallois
authors: Frances T
authors: FT
authors: Yen
authors: Olivier
authors: O
authors: Poch
authors: Marc
authors: M
authors: Guenneugues
authors: Gilles
authors: G
authors: Karcher
authors: Pierre
authors: P
authors: Oudet
authors: Bernard E
authors: BE
authors: Bihain
mesh_terms: D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D020224:Expressed Sequence Tags; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014746:Vimentin / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D014746:Vimentin