Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2007

Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis.

Marie Brulliard
  • Fonction : Auteur
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  • IdRef : 136765440
Dalia Lorphelin
  • Fonction : Auteur
Olivier Collignon
Walter Lorphelin
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Benoit Thouvenot
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  • PersonId : 759046
  • IdRef : 084129735
Emmanuel Gothié
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Sandrine Jacquenet
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  • IdRef : 152325506
Virginie Ogier
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  • IdRef : 070219761
Olivier Roitel
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  • PersonId : 759048
  • IdRef : 145174131
Frances T Yen
Marc Guenneugues
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Bernard E Bihain
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Résumé

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.

Dates et versions

hal-00190918 , version 1 (23-11-2007)

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Citer

Marie Brulliard, Dalia Lorphelin, Olivier Collignon, Walter Lorphelin, Benoit Thouvenot, et al.. Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis.. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (18), pp.7522-7. ⟨10.1073/pnas.0611076104⟩. ⟨hal-00190918⟩
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