M. Jinek, K. Chylinski, I. Fonfara, M. Hauer, J. A. Doudna et al., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity, Science, vol.337, issue.6096, pp.816-821, 2012.

G. Gasiunas, R. Barrangou, P. Horvath, and V. Siksnys, Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria, Proc. Natl. Acad. Sci. U.S.A, vol.109, issue.39, pp.2579-2586, 2012.

L. Cong, F. A. Ran, D. Cox, S. Lin, R. Barretto et al., Multiplex genome engineering using CRISPR/Cas systems, Science, vol.339, issue.6121, pp.819-823, 2013.

P. Mali, L. Yang, K. M. Esvelt, J. Aach, M. Guell et al., RNA-guided human genome engineering via Cas9, Science, vol.339, issue.6121, pp.823-826, 2013.

P. D. Hsu, E. S. Lander, and F. Zhang, Development and applications of CRISPR-Cas9 for genome engineering, Cell, vol.157, issue.6, pp.1262-1278, 2014.

J. A. Doudna, E. Charpentier, and G. Editing, The new frontier of genome engineering with CRISPR-Cas9, Science, vol.346, issue.6213, p.1258096, 2014.

J. D. Sander and J. K. Joung, CRISPR-Cas systems for editing, regulating and targeting genomes, Nat. Biotechnol, vol.32, issue.4, pp.347-355, 2014.

C. Kandoth, M. D. Mclellan, F. Vandin, K. Ye, B. Niu et al., Mutational landscape and significance across 12 major cancer types, Nature, vol.502, issue.7471, pp.333-339, 2013.

B. Vogelstein, N. Papadopoulos, V. E. Velculescu, S. Zhou, L. A. Diaz et al., Cancer genome landscapes, vol.339, issue.6127, pp.1546-1558, 2013.

A. Malina, J. R. Mills, R. Cencic, Y. Yan, J. Fraser et al., Repurposing CRISPR/Cas9 for in situ functional assays, Genes Dev, vol.27, issue.23, pp.2602-2614, 2013.

J. Albers, C. Danzer, M. Rechsteiner, H. Lehmann, L. P. Brandt et al., A versatile modular vector system for rapid combinatorial mammalian genetics, J. Clin. Invest, vol.125, issue.4, pp.1603-1619, 2015.

C. Chen, Y. Liu, A. R. Rappaport, T. Kitzing, N. Schultz et al., MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia, Cancer Cell, vol.25, issue.5, pp.652-665, 2014.

A. Harrod, J. Fulton, V. T. Nguyen, M. Periyasamy, L. Ramos-garcia et al., Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer, Oncogene, 2016.

J. E. Neggers, T. Vercruysse, M. Jacquemyn, E. Vanstreels, E. Baloglu et al., Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by CRISPR/Cas9 genome editing, Chem. Biol, vol.22, issue.1, pp.107-116, 2015.

O. Shalem, N. E. Sanjana, E. Hartenian, X. Shi, D. A. Scott et al., Genome-scale CRISPR-Cas9 knockout screening in human cells, Science, vol.343, issue.6166, pp.84-87, 2014.

S. Konermann, M. D. Brigham, A. E. Trevino, J. Joung, O. O. Abudayyeh et al., Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex, Nature, vol.517, issue.7536, pp.583-588, 2015.

N. E. Sanjana, J. Wright, K. Zheng, O. Shalem, P. Fontanillas et al., Highresolution interrogation of functional elements in the noncoding genome, Science, vol.353, issue.6307, pp.1545-1549, 2016.

Z. Siprashvili, D. E. Webster, D. Johnston, R. M. Shenoy, A. J. Ungewickell et al., The noncoding RNAs SNORD50A and SNORD50B bind K-Ras and are recurrently deleted in human cancer, Nat. Genet, vol.48, issue.1, pp.53-58, 2016.

K. Kataoka, Y. Shiraishi, Y. Takeda, S. Sakata, M. Matsumoto et al., Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers, Nature, vol.534, issue.7607, pp.402-406, 2016.

P. S. Choi and M. Meyerson, Targeted genomic rearrangements using CRISPR/Cas technology, Nat. Commun, vol.5, p.3728, 2014.

R. Torres, M. C. Martin, A. Garcia, J. C. Cigudosa, J. C. Ramirez et al., Engineering human tumour-associated chromosomal translocations with the RNA-guided CRISPR-Cas9 system, Nat. Commun, vol.5, p.3964, 2014.

M. Matano, S. Date, M. Shimokawa, A. Takano, M. Fujii et al., Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids, Nat. Med, vol.21, issue.3, pp.256-262, 2015.

J. Drost, R. H. Van-jaarsveld, B. Ponsioen, C. Zimberlin, R. Van-boxtel et al., Sequential cancer mutations in cultured human intestinal stem cells, Nature, vol.521, issue.7550, pp.43-47, 2015.

E. R. Fearon and B. Vogelstein, A genetic model for colorectal tumorigenesis, Cell, vol.61, issue.5, pp.759-767, 1990.

T. Sato, R. G. Vries, H. J. Snippert, M. Van-de-wetering, N. Barker et al., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche, Nature, vol.459, issue.7244, pp.262-265, 2009.

D. Heckl, M. S. Kowalczyk, D. Yudovich, R. Belizaire, R. V. Puram et al., Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing, Nat. Biotechnol, vol.32, issue.9, pp.941-946, 2014.

S. Chen, N. E. Sanjana, K. Zheng, O. Shalem, K. Lee et al., Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis, Cell, vol.160, issue.6, pp.1246-1260, 2015.

W. Xue, S. Chen, H. Yin, T. Tammela, T. Papagiannakopoulos et al., CRISPR-mediated direct mutation of cancer genes in the mouse liver, Nature, vol.514, issue.7522, pp.380-384, 2014.

M. Zuckermann, V. Hovestadt, C. B. Knobbe-thomsen, M. Zapatka, P. A. Northcott et al., Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling, Nat. Commun, vol.6, p.7391, 2015.

F. J. Sanchez-rivera, T. Papagiannakopoulos, R. Romero, T. Tammela, M. R. Bauer et al., Rapid modelling of cooperating genetic events in cancer through somatic genome editing, Nature, vol.516, issue.7531, pp.428-431, 2014.

D. Maddalo, E. Manchado, C. P. Concepcion, C. Bonetti, J. A. Vidigal et al., In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system, Nature, vol.516, issue.7531, pp.423-427, 2014.

R. B. Blasco, E. Karaca, C. Ambrogio, T. C. Cheong, E. Karayol et al., Simple and rapid in vivo generation of chromosomal rearrangements using CRISPR/Cas9 technology, Cell Rep, vol.9, issue.4, pp.1219-1227, 2014.

P. K. Mazur, A. Herner, S. S. Mello, M. Wirth, S. Hausmann et al., Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma, Nat. Med, vol.21, issue.10, pp.1163-1171, 2015.

R. J. Platt, S. Chen, Y. Zhou, M. J. Yim, L. Swiech et al., CRISPRCas9 knockin mice for genome editing and cancer modeling, Cell, vol.159, issue.2, pp.440-455, 2014.

S. H. Chiou, I. P. Winters, J. Wang, S. Naranjo, C. Dudgeon et al., Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing, Genes Dev, vol.29, issue.14, pp.1576-1585, 2015.

S. Annunziato, S. M. Kas, M. Nethe, H. Yucel, J. Bravo et al., Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland, Genes Dev, vol.30, issue.12, pp.1470-1480, 2016.

L. E. Dow, J. Fisher, K. P. O'rourke, A. Muley, E. R. Kastenhuber et al., Inducible in vivo genome editing with CRISPR-Cas9, Nat. Biotechnol, vol.33, issue.4, pp.390-394, 2015.

F. A. Ran, P. D. Hsu, C. Y. Lin, J. S. Gootenberg, S. Konermann et al., Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity, Cell, vol.154, issue.6, pp.1380-1389, 2013.

R. J. Gillies, D. Verduzco, and R. A. Gatenby, Evolutionary dynamics of carcinogenesis and why targeted therapy does not work, Nat. Rev. Cancer, vol.12, issue.7, pp.487-493, 2012.

M. Greaves and C. C. Maley, Clonal evolution in cancer, Nature, vol.481, issue.7381, pp.306-313, 2012.

N. Mcgranahan and C. Swanton, Biological and therapeutic impact of intratumor heterogeneity in cancer evolution, Cancer Cell, vol.27, issue.1, pp.15-26, 2015.

A. Marusyk and K. Polyak, Tumor heterogeneity: causes and consequences, Biochim. Biophys. Acta, vol.1805, issue.1, pp.105-117, 2010.

M. Kleppe and R. L. Levine, Tumor heterogeneity confounds and illuminates: assessing the implications, Nat. Med, vol.20, issue.4, pp.342-344, 2014.

A. A. Alizadeh, V. Aranda, A. Bardelli, C. Blanpain, C. Bock et al., Toward understanding and exploiting tumor heterogeneity, Nat. Med, vol.21, issue.8, pp.846-853, 2015.

Y. Lin, T. J. Cradick, M. T. Brown, H. Deshmukh, P. Ranjan et al., CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences, Nucleic Acids Res, vol.42, issue.11, pp.7473-7485, 2014.

X. Wang, Y. Wang, X. Wu, J. Wang, Y. Wang et al., Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors, Nat. Biotechnol, vol.33, issue.2, pp.175-178, 2015.

A. Guernet, S. K. Mungamuri, D. Cartier, R. Sachidanandam, A. Jayaprakash et al., CRISPR-barcoding for intratumor genetic heterogeneity modeling and functional analysis of oncogenic driver mutations, Mol. Cell, vol.63, issue.3, pp.526-538, 2016.

L. V. Nguyen, C. L. Cox, P. Eirew, D. J. Knapp, D. Pellacani et al., DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts, Nat. Commun, vol.5, p.5871, 2014.

L. V. Nguyen, D. Pellacani, S. Lefort, N. Kannan, T. Osako et al., Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells, Nature, 2015.

H. E. Bhang, D. A. Ruddy, V. Radhakrishna, J. X. Caushi, R. Zhao et al., Studying clonal dynamics in response to cancer therapy using high-complexity barcoding, Nat. Med, vol.21, issue.5, pp.440-448, 2015.

A. N. Hata, M. J. Niederst, H. L. Archibald, M. Gomez-caraballo, F. M. Siddiqui et al., Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition, Nat. Med, vol.22, issue.3, pp.262-269, 2016.