Giovanni Tonon

Functional genomics of cancer

Giovanni Tonon, Head of Unit

tonon.giovanni@hsr.it


While great progress has been made in recent years toward a better understanding of the molecular basis and in the development of more effective preventive, diagnostic and therapeutic tools, prognosis for many different forms of cancers remains dismal. High-throughput genomic technologies have shed light on the multifaceted lesions, both genetic and epigenetic, that characterize tumor cells and reinforced the notion that only a comprehensive understanding of these lesions would allow a more incisive and ultimately effective cancer treatment. The goal of the laboratory of Functional Genomics of Cancer is to contribute to unravel the genes and mechanisms causative of a selected group of epithelial and hematological cancers, using the most recent genomic and epigenomic technologies, and to rigorously validate the resultsemerging from these analysis. Cancer is a devastating burden for patients and their families. Our ambition is to provide the scientific community with a fully validated set of genes and pathways that could become targets for focused therapeutic strategies.

Selected publications

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(5):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(6):599-606. doi: 10.1038/nm.3562. Epub 2014 May 11. PMID: 24813251

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.

Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen A, Perry SR, Tonon G, Chu GC, Ding Z, Stommel JM, Dunn KL, Wiedemeyer R, You MJ, Brennan C, Wang YA, Ligon KL, Wong WH, Chin L, DePinho RA. p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature. 2008. 455:1129-33.

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.

Tonon G. From oncogene to network addiction: the new frontier of cancer genomics and therapeutics. Future Oncol. 2008. 4: 569-77.

Tonon G, Anderson, KC. Moving toward individualized cancer therapies. Clin Cancer Res. 2008. 14: 4682-4.

Tonon G. Molecular Pathogenesis of Multiple Myeloma. Hematology/Oncology Clinics of North America.  2007. 21:985-1006.

Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis and the role of the bone marrow microenvironment to identify new therapeutic targets. Nature Reviews of Cancer. 2007. 7: 585-98.

Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS, Munshi N, Horner J, Ivanova EV, Protopopov A, Anderson KC, Tonon G, DePinho RA. The differentiation and stress response factor, XBP-1, drives multiple myeloma pathogenesis. Cancer Cell. 2007. 11:349-60.

Podar K, Tonon G, Sattler M, Catley LP, Tai YT, Yasui H, LeGouill S, Kumar R, Pandite LN, Hideshima T, Chauhan D, Anderson KC. The small- molecule VEGF- receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc Natl Acad Sci U S A.  2006. 103:19478-83.

*Carrasco DR, *Tonon G, *Huang Y, Zhang Y, Sinha R, Feng B, Stewart JP, Zhan F, Khatry D, Protopopova M, Protopopov A, Sukhdeo K, Hanamura I, Stephens O, Barlogie B, Anderson KC, Chin L, Shaughnessy, Jr. JD, Brennan C and DePinho RA. High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell. 2006. 9:313-25.

Tonon G, Brennan C, Protopopov A, Maulik G, Feng B, Zhang Y, Khatry DB, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, Wong KK, DePinho RA. Common and Contrasting Genomic Profiles Among The Major Human Lung Cancer Subtypes. Cold Spring Harb Symp Quant Biol. 2005. 70:11-24.

*Tonon G, *Wong KK, *Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, DePinho RA. High resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A. 2005. 102:9625-30.

*Roschke AV, *Lababidi S, *Tonon G, Gehlhaus KS, Bussey K, Weinstein JN, Kirsch IR. Karyotypic “state” as a potential determinant for anticancer drug discovery. Proc Natl Acad Sci USA. 2005. 102: 2964-69.

*Tonon G, *Modi S, *Wu L, Kubo A, Coxon AB, Komiya T, O’Neil K, Stover K, El-Naggar A, Griffin JD, Kirsch IR, Kaye FJ.translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Nat Genet. 2003. 33:208-13.

*Roschke AV, *Tonon G, Gehlhaus KS, McTyre N, Bussey KJ, Lababidi S, Scudiero DA, Weinstein JN, Kirsch IR. Karyotypic complexity of the NCI-60 drug-screening panel. Cancer Res. 2003. 63:8634-47.

 


Home
| Curriculum | Lab members | Research | Publications | Links