Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma

Nature Genetics - Tập 48 Số 2 - Trang 183-188 - 2016
Jessica Okosun1, Rachel L. Wolfson2, Jun Wang3, Shamzah Araf1, Lucy Wilkins1, Brian M. Castellano4, Leire Escudero‐Ibarz5, Ahad Al Seraihi1, Julia Richter6, Stephan Wolf7, Alejo Efeyan2, Sameena Iqbal1, Janet Matthews1, Andrew Clear1, José Afonso Guerra‐Assunção3, Csaba Bödör8, Hilmar Quentmeier9, Christopher Mansbridge10, Peter Johnson10, Andrew Davies10, Jonathan C. Strefford10, Graham Packham10, Sharon Barrans11, Andrew Jack11, Ming‐Qing Du5, Maria Calaminici1, T. Andrew Lister1, Rebecca Auer1, Silvia Montoto1, John G. Gribben1, Reiner Siebert6, Claude Chelala3, Roberto Zoncu4, David M. Sabatini12, Jude Fitzgibbon1
1Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
2Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
3Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
4Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA
5Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK
6Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel and Christian Albrechts University Kiel, Kiel, Germany
7Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, Leipzig, Germany
81st Department of Pathology and Experimental Cancer Research, MTA-SE Lendulet Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary
9Leibniz Institute, DSMZ – German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
10Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK
11Haematological Malignancy Diagnostic Service, St. James’s Institute of Oncology, Leeds, UK
12Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

Swenson, W.T. et al. Improved survival of follicular lymphoma patients in the United States. J. Clin. Oncol. 23, 5019–5026 (2005).

Okosun, J. et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat. Genet. 46, 176–181 (2014).

Pasqualucci, L. et al. Genetics of follicular lymphoma transformation. Cell Reports 6, 130–140 (2014).

Karube, K. et al. Recurrent mutations of NOTCH genes in follicular lymphoma identify a distinctive subset of tumours. J. Pathol. 234, 423–430 (2014).

Yildiz, M. et al. Activating STAT6 mutations in follicular lymphoma. Blood 125, 668–679 (2015).

Morin, R.D. et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat. Genet. 42, 181–185 (2010).

Pasqualucci, L. et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 471, 189–195 (2011).

Compagno, M. et al. Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma. Nature 459, 717–721 (2009).

Lenz, G. et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319, 1676–1679 (2008).

Lohr, J.G. et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. USA 109, 3879–3884 (2012).

Ngo, V.N. et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 470, 115–119 (2011).

Morin, R.D. et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 476, 298–303 (2011).

Pasqualucci, L. et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat. Genet. 43, 830–837 (2011).

Bödör, C. et al. EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood 122, 3165–3168 (2013).

Green, M.R. et al. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood 121, 1604–1611 (2013).

Beà, S. et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc. Natl. Acad. Sci. USA 110, 18250–18255 (2013).

Landau, D.A. et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 152, 714–726 (2013).

Lohr, J.G. et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 25, 91–101 (2014).

Morin, R.D. et al. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood 122, 1256–1265 (2013).

Schmitz, R. et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature 490, 116–120 (2012).

Gao, J. et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6, pl1 (2013).

Nakashima, N., Noguchi, E. & Nishimoto, T. Saccharomyces cerevisiae putative G protein, Gtr1p, which forms complexes with itself and a novel protein designated as Gtr2p, negatively regulates the Ran/Gsp1p G protein cycle through Gtr2p. Genetics 152, 853–867 (1999).

Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M. & Nishimoto, T. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J. Biol. Chem. 276, 7246–7257 (2001).

Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T.P. & Guan, K.L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10, 935–945 (2008).

Sancak, Y. et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320, 1496–1501 (2008).

Bar-Peled, L. et al. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340, 1100–1106 (2013).

Bar-Peled, L., Schweitzer, L.D., Zoncu, R. & Sabatini, D.M. Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1. Cell 150, 1196–1208 (2012).

Sancak, Y. et al. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290–303 (2010).

Zoncu, R. et al. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H+-ATPase. Science 334, 678–683 (2011).

Rebsamen, M. et al. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 519, 477–481 (2015).

Wang, S. et al. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347, 188–194 (2015).

Forgac, M. Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat. Rev. Mol. Cell Biol. 8, 917–929 (2007).

Jansen, E.J. & Martens, G.J. Novel insights into V-ATPase functioning: distinct roles for its accessory subunits ATP6AP1/Ac45 and ATP6AP2/(pro) renin receptor. Curr. Protein Pept. Sci. 13, 124–133 (2012).

Iadevaia, V., Huo, Y., Zhang, Z., Foster, L.J. & Proud, C.G. Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis. Biochem. Soc. Trans. 40, 168–172 (2012).

Ben-Sahra, I., Howell, J.J., Asara, J.M. & Manning, B.D. Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science 339, 1323–1328 (2013).

Tsun, Z.Y. et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol. Cell 52, 495–505 (2013).

Feig, L.A. & Cooper, G.M. Relationship among guanine nucleotide exchange, GTP hydrolysis, and transforming potential of mutated ras proteins. Mol. Cell. Biol. 8, 2472–2478 (1988).

Feig, L.A. Tools of the trade: use of dominant-inhibitory mutants of Ras-family GTPases. Nat. Cell Biol. 1, E25–E27 (1999).

John, J. et al. Kinetic and structural analysis of the Mg2+-binding site of the guanine nucleotide–binding protein p21H-ras. J. Biol. Chem. 268, 923–929 (1993).

Hara, K. et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273, 14484–14494 (1998).

Nicklin, P. et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136, 521–534 (2009).

Hoffenberg, S. et al. Functional and structural interactions of the Rab5 D136N mutant with xanthine nucleotides. Biochem. Biophys. Res. Commun. 215, 241–249 (1995).

Schmidt, G. et al. Biochemical and biological consequences of changing the specificity of p21ras from guanosine to xanthosine nucleotides. Oncogene 12, 87–96 (1996).

Farnsworth, C.L. & Feig, L.A. Dominant inhibitory mutations in the Mg2+-binding site of RasH prevent its activation by GTP. Mol. Cell. Biol. 11, 4822–4829 (1991).

Lai, C.C., Boguski, M., Broek, D. & Powers, S. Influence of guanine nucleotides on complex formation between Ras and CDC25 proteins. Mol. Cell. Biol. 13, 1345–1352 (1993).

Proud, C.S. Guanine nucleotides, protein phosphorylation and the control of translation. Trends Biochem. Sci. 11, 73–77 (1986).

Krengel, U. et al. Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell 62, 539–548 (1990).

Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

DePristo, M.A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011).

Koboldt, D.C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).

Dayem Ullah, A.Z., Lemoine, N.R. & Chelala, C. SNPnexus: a web server for functional annotation of novel and publicly known genetic variants (2012 update). Nucleic Acids Res. 40, W65–W70 (2012).

Saitou, N. & Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406–425 (1987).

Van Loo, P. et al. Allele-specific copy number analysis of tumors. Proc. Natl. Acad. Sci. USA 107, 16910–16915 (2010).

Langmead, B. & Salzberg, S.L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).

Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).

Law, C.W., Chen, Y., Shi, W. & Smyth, G.K. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).

Ritchie, M.E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550 (2005).

Boussif, O. et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. USA 92, 7297–7301 (1995).