Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer

Nature Methods

Volumn 10, Issue 2, 2013, Pages 155-161

  Ranzani, Marco ^a   Cesana, Daniela ^a   Bartholomae, Cynthia C ^b   Sanvito, Francesca ^c   Pala, Mauro ^d   Benedicenti, Fabrizio ^a   Gallina, Pierangela ^a   Sergi, Lucia Sergi ^a   Merella, Stefania ^a   Bulfone, Alessandro ^d   Doglioni, Claudio ^c,e   Von Kalle, Christof ^b   Kim, Yoon Jun ^f   Schmidt, Manfred ^b   Tonon, Giovanni ^c   Naldini, Luigi ^a,e   Montini, Eugenio ^a  

^a SAN RAFFAELE SCIENTIFIC INSTITUTE   (Italy)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c SAN RAFFAELE HOSPITAL   (Italy)

^d BioFlag Ltd   (Italy)

^e VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^f Seoul National University College of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

LENTIVIRUS VECTOR; TRANSCRIPTOME; WNT PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAF GENE; CONTROLLED STUDY; FIGN GENE; GENE; GENE AMPLIFICATION; GENE DELETION; GENE IDENTIFICATION; IN VIVO STUDY; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; MOUSE; MUTAGENESIS; NEWBORN; NONHUMAN; NUCLEOTIDE SEQUENCE; ONCOGENE; OUTCOME ASSESSMENT; OXIDATIVE PHOSPHORYLATION; PENETRANCE; PREDICTIVE VALUE; PRIORITY JOURNAL; RTL1 GENE; SOS1 GENE; UPREGULATION; VALIDATION STUDY; VIRUS DNA CELL DNA INTERACTION; VIRUS GENOME; VIRUS REPLICATION;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CYCLIN-DEPENDENT KINASE INHIBITOR P16; GENETIC VECTORS; HUMANS; LENTIVIRUS; LIVER NEOPLASMS; MICE; MUTAGENESIS, INSERTIONAL; ONCOGENES; PREALBUMIN; PTEN PHOSPHOHYDROLASE; RECEPTOR, INTERFERON ALPHA-BETA;

EID: 84873409442     PISSN: 15487091     EISSN: 15487105     Source Type: Journal    
DOI: 10.1038/nmeth.2331     Document Type: Article

References (59)

1. Stratton, M.R., Campbell, P.J. & Futreal, P.A. The cancer genome. Nature 458, 719-724 (2009).
2. Kool, J. & Berns, A. High-throughput insertional mutagenesis screens in mice to identify oncogenic networks. Nat. Rev. Cancer 9, 389-399 (2009).
3. Montini, E. et al. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J. Clin. Invest. 119, 964-975 (2009).
4. Naldini, L., Blomer, U., Gage, F.H., Trono, D. & Verma, I.M. Effcient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc. Natl. Acad. Sci. USA 93, 11382-11388 (1996).
5. Croci, C. et al. Cerebellar neurons and glial cells are transducible by lentiviral vectors without decrease of cerebellar functions. Dev. Neurosci. 28, 216-221 (2006).
6. Dolcetta, D. et al. Design and optimization of lentiviral vectors for transfer of GALC expression in Twitcher brain. J. Gene Med. 8, 962-971 (2006).
7. Céfaï, D. et al. Multiply attenuated, self-inactivating lentiviral vectors effciently transduce human coronary artery cells in vitro and rat arteries in vivo. J. Mol. Cell. Cardiol. 38, 333-344 (2005).
8. Bonci, D. et al. 'Advanced' generation lentiviruses as effcient vectors for cardiomyocyte gene transduction in vitro and in vivo. Gene Ther. 10, 630-636 (2003).
9. Buckley, S.M. et al. Lentiviral transduction of the murine lung provides effcient pseudotype and developmental stage-dependent cell-specifc transgene expression. Gene Ther. 15, 1167-1175 (2008).
10. Di Nunzio, F. et al. Correction of laminin-5 defciency in human epidermal stem cells by transcriptionally targeted lentiviral vectors. Mol. Ther. 16, 1977-1985 (2008).
11. Tedesco, F.S. et al. Transplantation of genetically corrected human iPSC-derived progenitors in mice with limb-girdle muscular dystrophy. Sci. Transl. Med. 4, 140ra189 (2012).
12. Follenzi, A., Sabatino, G., Lombardo, A., Boccaccio, C. & Naldini, L. Effcient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum. Gene Ther. 13, 243-260 (2002).
13. Serrano, M. et al. Role of the INK4a locus in tumor suppression and cell mortality. Cell 85, 27-37 (1996).
14. Brown, B.D. et al. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 109, 2797-2805 (2007).
15. Tannapfel, A. et al. INK4a-ARF alterations and p53 mutations in hepatocellular carcinomas. Oncogene 20, 7104-7109 (2001).
16. Farazi, P.A. & DePinho, R.A. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat. Rev. Cancer 6, 674-687 (2006).
17. Horie, Y. et al. Hepatocyte-specifc Pten defciency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest. 113, 1774-1783 (2004).
18. Hu, T.H. et al. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 97, 1929-1940 (2003).
19. Vigna, E. et al. Effcient Tet-dependent expression of human factor IX in vivo by a new self-regulating lentiviral vector. Mol. Ther. 11, 763-775 (2005).
20. Abel, U. et al. Real-time defnition of non-randomness in the distribution of genomic events. PLoS ONE 2, e570 (2007).
21. Wu, X., Luke, B.T. & Burgess, S.M. Redefning the common insertion site. Virology 344, 292-295 (2006).
22. Collier, L.S., Carlson, C.M., Ravimohan, S., Dupuy, A.J. & Largaespada, D.A. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature 436, 272-276 (2005).
23. Gureasko, J. et al. Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless. Proc. Natl. Acad. Sci. USA 107, 3430-3435 (2010).
24. Brown, B.D. et al. A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood 110, 4144-4152 (2007).
25. Wurmbach, E. et al. Genome-wide molecular profles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology 45, 938-947 (2007).
26. Chen, X. et al. Gene expression patterns in human liver cancers. Mol. Biol. Cell 13, 1929-1939 (2002).
27. Woo, H.G. et al. Identifcation of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. Cancer Res. 70, 3034-3041 (2010).
28. ARF-and p53-defcient mice identifes cancer genes and their collaborative networks. Cell 133, 727-741 (2008).
29. Starr, T.K. et al. A transposon-based genetic screen in mice identifes genes altered in colorectal cancer. Science 323, 1747-1750 (2009).
30. Rad, R. et al. PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice. Science 330, 1104-1107 (2010).
31. Keng, V.W. et al. A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nat. Biotechnol. 27, 264-274 (2009).
32. Colombino, M. et al. BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy. Cell Death Dis. 3, e259 (2012).
33. Ciampi, R. et al. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest. 115, 94-101 (2005).
34. Palanisamy, N. et al. Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat. Med. 16, 793-798 (2010).
35. Guichard, C. et al. Integrated analysis of somatic mutations and focal copy-number changes identifes key genes and pathways in hepatocellular carcinoma. Nat. Genet. 44, 694-698 (2012).
36. Schneider, A., Mehmood, T., Pannetier, S. & Hanauer, A. Altered ERK/MAPK signaling in the hippocampus of the mrsk2-KO mouse model of Coffn-Lowry syndrome. J. Neurochem. 119, 447-459 (2011).
37. Douville, E. & Downward, J. EGF induced SOS phosphorylation in PC12 cells involves P90 RSK-2. Oncogene 15, 373-383 (1997).
38. Llovet, J.M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378-390 (2008).
39. Donsante, A. et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science 317, 477 (2007).
40. Dupuy, A.J. et al. A modifed sleeping beauty transposon system that can be used to model a wide variety of human cancers in mice. Cancer Res. 69, 8150-8156 (2009).
41. Montini, E. et al. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat. Biotechnol. 24, 687-696 (2006).
42. Themis, M. et al. Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice. Mol. Ther. 12, 763-771 (2005).
43. Follenzi, A., Ailles, L.E., Bakovic, S., Geuna, M. & Naldini, L. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat. Genet. 25, 217-222 (2000).
44. Kim, W.Y. & Sharpless, N.E. The regulation of INK4/ARF in cancer and aging. Cell 127, 265-275 (2006).
45. Müller, U. et al. Functional role of type I and type II interferons in antiviral defense. Science 264, 1918-1921 (1994).
46. Clawson, G.A. Mechanisms of carbon tetrachloride hepatotoxicity. Pathol. Immunopathol. Res. 8, 104-112 (1989).
47. Weber, L.W., Boll, M. & Stampf, A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit. Rev. Toxicol. 33, 105-136 (2003).
48. Bosman, F.T., Carneiro, F., Hruban, R.H. & Theise, N.D. WHO Classifcation of Tumours of the Digestive System 4th edn. (World Health Organization, 2010).
49. Ishak, K.G., Goodman, Z.D. & Stocker, J.T. Atlas of Tumor Pathology: Tumors of the Liver and Intrahepatic Bile Ducts (Armed Forces Institute of Pathology; Washington, DC; 2001).
50. Hadjantonakis, A.K., Gertsenstein, M., Ikawa, M., Okabe, M. & Nagy, A. Generating green fuorescent mice by germline transmission of green fuorescent ES cells. Mech. Dev. 76, 79-90 (1998).
51. Schmidt, M. et al. A model for the detection of clonality in marked hematopoietic stem cells. Ann. NY Acad. Sci. 938, 146-156 (2001).
52. Ott, M.G. et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat. Med. 12, 401-409 (2006).
53. + cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial. Blood 105, 2699-2706 (2005).
54. Schmidt, M. et al. Detection and direct genomic sequencing of multiple rare unknown fanking DNA in highly complex samples. Hum. Gene Ther. 12, 743-749 (2001).
55. Schmidt, M. et al. High-resolution insertion-site analysis by linear amplifcation-mediated PCR (LAM-PCR). Nat. Methods 4, 1051-1057 (2007).
56. Pfaff, M.W. A new mathematical model for relative quantifcation in real-time RT-PCR. Nucleic Acids Res. 29, e45 (2001).
57. Zhao, S. & Fernald, R.D. Comprehensive algorithm for quantitative realtime polymerase chain reaction. J. Comput. Biol. 12, 1047-1064 (2005).
58. Hellemans, J., Mortier, G., De Paepe, A., Speleman, F. & Vandesompele, J. qBase relative quantifcation framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol. 8, R19 (2007).
59. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profles. Proc. Natl. Acad. Sci. USA 102, 15545-15550 (2005).