Proteogenomic associated to MALDI MSI for targeting alternative proteins involved in oncological processes

Support : Siric OncoLille, La Ligue Contre Le Cancer, Canceropole Nord-Ouest

Partners : Oncovet Clinical Research (OCR), Sherbooke Univ, Pr. X. Roucou)

 With the recent advances of high throughput sequencing in the field of genomics and mass spectrometry (MS) based proteomics, it has been shown that traditional computational genome annotation algorithms have underestimated the number of open reading frames (ORFs). Recent evidence has shown that small ORFs (smORFs) are present in RNAs including non-coding RNAs. Recently, PRISM has shown that many microproteins translated from smORFs can be detected in cancer including ovarian cancer and glioma. Even if their existence has been widely proven, their biological functions remain to be elucidated. Thus GHOST project  will respond to questions focusing on the role of microproteins and therefore their involvement in the glioma. Novel potential therapeutic targets can be identified and may not lead to tumor resistance or secondary effects of treatment. Additionally, large scale proteomics analysis combining microproteins and canonical proteins will provide more insights about patient profiles in response to specific treatments.

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Publications

Delcourt, V., Staskevicius, A., Salzet, M., Fournier, I., and Roucou, X. (2017) Small Proteins Encoded by Unannotated ORFs are Rising Stars of the Proteome, Confirming Shortcomings in Genome Annotations and Current Vision of an mRNA. Proteomics (in press)

Delcourt V, Brunelle M, Roy AV, Jacques JF, Salzet M, Fournier I, Roucou X. First evidence that a protein coded by a short ORF, not by the annotated CDS is the main gene product. Molecular and Cellualr Proteomics. (in press)

Delcourt, V., Franck, J., Quanico, J., Gimeno, J. P., Wisztorski, M., Raffo Romero, A., Kobeissy, F., Roucou, X., Salzet, M., and Fournier, I. (2017) Top-down microproteomics bridged to MALDI MS imaging reveals the molecular physiome of brain regions. Molecular & cellular proteomics : Molecular and Cellular Protemics 2018 17(2):357-372

Delcourt, V., Franck, J., Leblanc, E., Narducci, F., Robin, Y. M., Gimeno, J. P., Quanico, J., Wisztorski, M., Kobeissy, F., Jacques, J. F., Roucou, X., Salzet, M., and Fournier, I. (2017) Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer. EBioMedicine 21, 55-64

Mouilleron, H., Delcourt, V., and Roucou, X. (2016) Death of a dogma: eukaryotic mRNAs can code for more than one protein. Nucleic acids research 44, 14-23

Vanderperre, B., Lucier, J. F., Bissonnette, C., Motard, J., Tremblay, G., Vanderperre, S., Wisztorski, M., Salzet, M., Boisvert, F. M., and Roucou, X. (2013) Direct detection of alternative open reading frames translation products in human significantly expands the proteome. PloS one 8, e70698