Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity increases during carcinogenesis.
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| 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.
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| Authors | Marie Brulliard, Dalia Lorphelin, Olivier Collignon, Walter Lorphelin, Benoit Thouvenot, Emmanuel Gothié, Sandrine Jacquenet, Virginie Ogier, Olivier Roitel, Jean-Marie Monnez, Pierre Vallois, Frances T Yen, Olivier Poch, Marc Guenneugues, Gilles Karcher, Pierre Oudet, Bernard E Bihain |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 18 Pg. 7522-7 (May 01 2007) ISSN: 0027-8424 [Print] United States |
| PMID | 17452638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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