U830 – Genetics and Biology of Cancers

Teams in this unit study various aspects of tumour development. Two main strategies are being developed:

  • the direct study of human malignancies to better understand their physiopathological mechanisms,

  • the uses experimental models (cells or animals) to address specific aspects of oncogenesis.

A variety of genetic methods including microarray, genotyping and next-generation sequencing analyses are developed to characterise human tumours, as well as molecular biology, cell biology and transgenesis approaches to create and investigate models are being used.

The main research themes of the unit include:

  • The link between oncogenesis, stemness and cell differentiation, especially in neural and mesenchymal cell lineages, with the goal of establishing similarities and differences between the biology of the tumour cells and their corresponding normal cells,
  • The genetic alterations in cancer cells, in particular the mechanisms of genetic instability that may be a cause or a consequence of tumour development,
  • The role of oxidative stress in angiogenesis, cell aging and tumour development,
  • The changes in intracellular traffic and in the cytoskeleton that are associated with malignant transformation.

Key publications

Year of publication 2016

Tina Gruosso, Virginie Mieulet, Melissa Cardon, Brigitte Bourachot, Yann Kieffer, Flavien Devun, Thierry Dubois, Marie Dutreix, Anne Vincent-Salomon, Kyle Malcolm Miller, Fatima Mechta-Grigoriou (2016 Mar 24)

Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.

EMBO molecular medicine : 527-49 : DOI : 10.15252/emmm.201505891
Zhi-Yan Han, Wilfrid Richer, Paul Fréneaux, Céline Chauvin, Carlo Lucchesi, Delphine Guillemot, Camille Grison, Delphine Lequin, Gaelle Pierron, Julien Masliah-Planchon, André Nicolas, Dominique Ranchère-Vince, Pascale Varlet, Stéphanie Puget, Isabelle Janoueix-Lerosey, Olivier Ayrault, Didier Surdez, Olivier Delattre, Franck Bourdeaut (2016 Jan 29)

The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.

Nature communications : 10421 : DOI : 10.1038/ncomms10421
Luciana Batista, Brigitte Bourachot, Bogdan Mateescu, Fabien Reyal, Fatima Mechta-Grigoriou (2016 Jan 5)

Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through.

Nature communications : 8959 : DOI : 10.1038/ncomms9959

Year of publication 2015

Tina Gruosso, Camille Garnier, Sophie Abelanet, Yann Kieffer, Vincent Lemesre, Dorine Bellanger, Ivan Bieche, Elisabetta Marangoni, Xavier Sastre-Garau, Virginie Mieulet, Fatima Mechta-Grigoriou (2015 Oct 13)

MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas.

Nature communications : 8583 : DOI : 10.1038/ncomms9583
Angela Bellini, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Valérie Combaret, Eve Lapouble, Nathalie Clement, Herve Rubie, Estelle Thebaud, Pascal Chastagner, Anne Sophie Defachelles, Christophe Bergeron, Nimrod Buchbinder, Sophie Taque, Anne Auvrignon, Dominique Valteau-Couanet, Jean Michon, Isabelle Janoueix-Lerosey, Olivier Delattre, Gudrun Schleiermacher (2015 Feb 20)

Deep Sequencing Reveals Occurrence of Subclonal ALK Mutations in Neuroblastoma at Diagnosis.

Clinical cancer research : an official journal of the American Association for Cancer Research : 4913-21 : DOI : 10.1158/1078-0432.CCR-15-0423
Thomas F Eleveld, Derek A Oldridge, Virginie Bernard, Jan Koster, Leo Colmet Daage, Sharon J Diskin, Linda Schild, Nadia Bessoltane Bentahar, Angela Bellini, Mathieu Chicard, Eve Lapouble, Valérie Combaret, Patricia Legoix-Né, Jean Michon, Trevor J Pugh, Lori S Hart, JulieAnn Rader, Edward F Attiyeh, Jun S Wei, Shile Zhang, Arlene Naranjo, Julie M Gastier-Foster, Michael D Hogarty, Shahab Asgharzadeh, Malcolm A Smith, Jaime M Guidry Auvil, Thomas B K Watkins, Danny A Zwijnenburg, Marli E Ebus, Peter van Sluis, Anne Hakkert, Esther van Wezel, C Ellen van der Schoot, Ellen M Westerhout, Johannes H Schulte, Godelieve A Tytgat, M Emmy M Dolman, Isabelle Janoueix-Lerosey, Daniela S Gerhard, Huib N Caron, Olivier Delattre, Javed Khan, Rogier Versteeg, Gudrun Schleiermacher, Jan J Molenaar, John M Maris (2015 Jan 15)

Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations.

Nature genetics : 864-71 : DOI : 10.1038/ng.3333