Experimental oncology

Functional genomics of cancer

Group leader

Giovanni Tonon

The unit aims to define how oncogenes and tumor suppressors cause cancer. Functional genomics of cancer Unit has identified genes that are frequently altered in cancer and are implicated in epigenetics, RNA metabolism, DNA repair and cancer evolution. Leveraging upon the most advanced genomics techniques and more traditional molecular and cell biology approaches, the group strives to identify therapeutic opportunities to target these mutated genes.

Advanced search >

Selected publications

Tedesco M., Giannese F., Lazarević D., Giansanti V., Rosano D., Monzani S., ... & Tonon, G.. Chromatin Velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin. Nature Biotechnology, 2022, 40(2), 235-244.

Gaviraghi M, Vivori C, Pareja Sanchez Y, Invernizzi F, Cattaneo A, Santoliquido BM, Frenquelli M, Segalla S, Bachi A, Doglioni C, Pelechano V, Cittaro D, Tonon G. Tumor suppressor PNRC1 blocks rRNA maturation by recruiting the decapping complex to the nucleolus. EMBO J. 2018, doi: 10.15252/embj.201899179.

Ezponda T, Dupéré-Richer D, Will CM, Small EC, Varghese N, Patel T, Nabet B, Popovic R, Oyer J, Bulic M, Zheng Y, Huang X, Shah MY, Maji S, Riva A, Occhionorelli M, Tonon G, Kelleher N, Keats J, Licht JD. UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition. Cell Rep. 2017; 21(3):628-640.

Rondinelli B, Rosano D, Antonini E, Frenquelli M, Montanini L, Huang D, Segalla S, Yoshihara K, Amin SB, Lazarevic D, The BT, Verhaak RG, Futreal PA, Di Croce L, Chin L, Cittaro D, Tonon G. Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer. J Clin Invest. 2015; 125:4625-37.

Cottini F, Hideshima T, Suzuki R, Tai YT, Bianchini G, Richardson PG, Anderson KC, Tonon G. Synthetic lethal approaches exploiting DNA damage in aggressive myeloma. Cancer Discovery. 2015; 5:972-87.

Segalla S, Pivetti S, Todoerti K, Malgorzata A, Giuliani E, Lazzaro F, Volta V, Lazarevic D, Musco G, Muzi-Falconi M, Neri A, Biffo S, Tonon G. The ribonuclease DIS3 promotes let-7 miRNA maturation by degrading the pluripotency factor LIN28B mRNA. Nucleic Acids Res. 2015; 43:5182-93.

Rondinelli B, Schwerer H, Antonini E, Gaviraghi M, Lupi A, Frenquelli M, Cittaro D, Segalla S, Lemaitre JM, Tonon G. H3K4me3 demethylation by the histone demethylase KDM5C/JARID1C promotes DNA replication origin firing. Nucleic Acids Res. 2015; 43:2560-74.

Ntziachristos P, Tsirigos A, Welstead GG, Trimarchi T, Bakogianni S, Xu L, Loizou E, Holmfeldt L, Strikoudis A, King B, Mullanders J, Becksfort J, Nedjic J, Paietta E, Tallman MS, Rowe JM, Tonon G, Satoh T, Kruidenier L, Prinjha R, Akira S, Van Vlierberghe P, Ferrando AA, Jaenisch R, Mullighan CG, Aifantis I. Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature 2014; 514:513-7.

Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, Ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med. 2014; 20:599-606.

Ranzani M, Cesana D, Bartholomae CC, Sanvito F, Pala M, Benedicenti F, Gallina P, Sergi LS, Merella S, Bulfone A, Doglioni C, von Kalle C, Kim YJ, Schmidt M, Tonon G, Naldini L, Montini E. Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer. Nat Methods. 2013; 10:155-61.

Sahin E, Colla S, Liesa M, Moslehi J, Müller FL, Guo M, Cooper M, Kotton D, Fabian AJ, Walkey C, Maser RS, Tonon G, Foerster F, Xiong R, Wang YA, Shukla SA, Jaskelioff M, Martin ES, Heffernan TP, Protopopov A, Ivanova E, Mahoney JE, Kost-Alimova M, Perry SR, Bronson R, Liao R, Mulligan R, Shirihai OS, Chin L, Depinho RA. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011; 470:359-65.

van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C, Edkins S, Hardy C, O'Meara S, Teague J, Butler A, Hinton J, Latimer C, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Cole J, Forbes S, Jia M, Jones D, Kok CY, Leroy C, Lin ML, McBride DJ, Maddison M, Maquire S, McLay K, Menzies A, Mironenko T, Mulderrig L, Mudie L, Pleasance E, Shepherd R, Smith R, Stebbings L, Stephens P, Tang G, Tarpey PS, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Collins VP, Ichimura K, Law S, Wong J, Yuen ST, Leung SY, Tonon G, DePinho RA, Tai YT, Anderson KC, Kahnoski RJ, Massie A, Khoo SK, Teh BT, Stratton MR, Futreal PA. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009; 41: 521-3.

Ding L, Getz G, Wheeler DA, Mardis EA, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SH, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008; 455:1069-75.