UMR3348 – Stress génotoxique et cancer

Publications de l’unité

Année de publication : 2018

Wang X, Allen WE, Wright MA, Sylwestrak EL, Samusik N, Vesuna S, Evans K, Liu C, Ramakrishnan C, Liu J, Nolan GP*, Bava FA*, Deisseroth K*. *co-last, co-corresponding author (2018 Jun 23)

Three-dimensional intact-tissue sequencing of single-cell transcriptional states.

Science (New York, N.Y.) : DOI : eaat5691 En savoir plus
Résumé

Retrieving high-content gene-expression information while retaining 3D positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. Here we develop and apply a technology for 3D intact-tissue RNA sequencing, termed STARmap (Spatially-resolved Transcript Amplicon Readout Mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1,020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy and reproducibility. Moving to thick tissue blocks, we observed a molecularly-defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells), and discovered a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.

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Maria M Magiera, Puja Singh, Carsten Janke (2018 Jun 2)

SnapShot: Functions of Tubulin Posttranslational Modifications.

Cell : 1552-1552.e1 : DOI : S0092-8674(18)30644-5 En savoir plus
Résumé

Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological processes. To view this SnapShot, open or download the PDF.

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Maria M Magiera, Puja Singh, Sudarshan Gadadhar, Carsten Janke (2018 Jun 2)

Tubulin Posttranslational Modifications and Emerging Links to Human Disease.

Cell : 1323-1327 : DOI : S0092-8674(18)30595-6 En savoir plus
Résumé

Tubulin posttranslational modifications are currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders. Here, we review the latest advances in understanding the physiological roles of tubulin modifications and their links to a variety of pathologies.

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Sandrine M Caputo, Mélanie Léone, Francesca Damiola, Asa Ehlen, Aura Carreira, Pascaline Gaidrat, Alexandra Martins, Rita D Brandão, Ana Peixoto, Ana Vega, Claude Houdayer, Capucine Delnatte, Myriam Bronner, Danièle Muller, Laurent Castera, Marine Guillaud-Bataille, Inge Søkilde, Nancy Uhrhammer, Sophie Demontety, Hélène Tubeuf, Gaïa Castelain, , Uffe Birk Jensen, Ambre Petitalot, Sophie Krieger, Cédrick Lefol, Virginie Moncoutier, Nadia Boutry-Kryza, Henriette Roed Nielsen, Olga Sinilnikova, Dominique Stoppa-Lyonnet, Amanda B Spurdle, Manuel R Teixeira, Florence Coulet, Mads Thomassen, Etienne Rouleau (2018 May 1)

Full in-frame exon 3 skipping of confers high risk of breast and/or ovarian cancer.

Oncotarget : 17334-17348 : DOI : 10.18632/oncotarget.24671 En savoir plus
Résumé

Germline pathogenic variants in the gene are associated with a cumulative high risk of breast/ovarian cancer. Several variants result in complete loss of the exon-3 at the transcript level. The pathogenicity of these variants and the functional impact of loss of exon 3 have yet to be established. As a collaboration of the COVAR clinical trial group (France), and the ENIGMA consortium for investigating breast cancer gene variants, this study evaluated 8 variants resulting in complete deletion of exon 3. Clinical information for 39 families was gathered from Portugal, France, Denmark and Sweden. Multifactorial likelihood analyses were conducted using information from 293 patients, for 7 out of the 8 variants (including 6 intronic). For all variants combined the likelihood ratio in favor of causality was 4.39*10. These results provide convincing evidence for the pathogenicity of all examined variants that lead to a total exon 3 skipping, and suggest that other variants that result in complete loss of exon 3 at the molecular level could be associated with a high risk of cancer comparable to that associated with classical pathogenic variants in or gene. In addition, our functional study shows, for the first time, that deletion of exon 3 impairs the ability of cells to survive upon Mitomycin-C treatment, supporting lack of function for the altered BRCA2 protein in these cells. Finally, this study demonstrates that any variant leading to expression of only delta-exon 3 will be associated with an increased risk of breast and ovarian cancer.

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