Molecular Cytogenetics Unit

Sandra Rodríguez Head of Unit
T +34 917328000 (Ext 3340)
srodriguezp@cnio.es

Staff Scientists

Raúl Torres

Graduate Students

Pilar Puig

Technicians

M. Carmen Martín
Francisco José Moya

Recurrent chromosomal rearrangements are very common and well-known hallmarks of cancer. One of their main consequences is the creation of new chimeric genes as a result of the fusion of the coding sequences of 2 different genes. The research activity of the Molecular Cytogenetics and Genome Editing Unit (MC&GEU) is focused on increasing the knowledge about the genetics of tumours and the discovery of new therapeutic targets. With the combined used of CRISPR genome editing and cytogenetic technologies, we are creating human in vitro models that recapitulate chromosomal, genetic and epigenetic cancer alterations. The goal of the Unit is to provide the CNIO and external researchers with the latest technologies used in the fields of molecular cytogenetics and genome editing. The Unit is constantly implementing and developing new technologies in the gene editing field. We also participate in collaborative projects with clinical and basic science investigators at the CNIO and other institutes.

Publications

Xu-Monette ZY, Xiao M, Au Q, Padmanabhan R, Xu B, Hoe N, Rodríguez-Perales S, Torres-Ruiz R, Manyam GC, Visco C, Miao Y, Tan X, Zhang H, Tzankov A, Wang J, Dybkær K, Tam W, You H, Bhagat G, Hsi ED, Ponzoni M, Ferreri AJM, Møller MB, Piris MA, van Krieken JH, Winter JN, Westin JR, Pham LV, Medeiros LJ, Rassidakis GZ, Li Y, Freeman GJ, Young KH (2019). Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL. Cancer Immunol Res 7, 644-657.
Escudero-Paniagua B, Bartolomé RA, Rodríguez S, de Los Ríos V, Pintado L, Jaen M, Lafarga M, Fernández-Aceñero MJ, Casal J (2019). PAUF/ZG16B promotes colorectal cancer progression through alterations of the mitotic functions and the Wnt/ß-catenin pathway. Carcinogenesis (in press).
Torres-Ruiz R, Benítez-Burraco A, Martínez-Lage M, Rodríguez-Perales S, García-Bellido P (2019). Functional characterization of two enhancers located downstream FOXP2. BMC Med Genet. 20, 65.
Bonafont J, Mencía Á, García M, Torres R, Rodríguez S, Carretero M, Chacón-Solano E, Modamio-Høybjør S, Marinas L, León C, Escamez MJ, Hausser I, Del Río M, Murillas R, Larcher F (2019). Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing. Mol Ther (in press).
Brandt M, Grazioso TP, Fawal MA, Tummala KS, Torres-Ruiz R, Rodriguez-Perales S, Perna C , Djouder N (2018). mTORC1 inactivation promotes colitis-induced colorectal cancer. Cell Metab 27, 118-135.
Oldrini B, Curiel-García Á, Marques C, Matia V, Uluçkan Ö, Graña-Castro O, Torres-Ruiz R, Rodriguez-Perales S, Huse JT, Squatrito M (2018). Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling. Nat Commun 9, 1466.
Sánchez-Hernández S, Gutierrez-Guerrero A, Martín-Guerra R, Cortijo-Gutierrez M, Tristán-Manzano M, Rodriguez-Perales S, Sanchez L, Garcia-Perez JL, Chato-Astrain J, Fernandez-Valades R, Carrillo-Galvez AB, Anderson P, Montes R, Real PJ, Martin F, Benabdellah K (2018). The IS2 Element Improves Transcription Efficiency of Integration-Deficient Lentiviral Vector Episomes. Molecular Therapy-Nucleic Acids 13, 16-28.
Martinez-Lage M, Puig-Serra P, Menendez P, Torres-Ruiz R, Rodriguez-Perales S (2018). CRISPR/Cas9 for Cancer Therapy: Hopes and Challenges. Biomedicines 6, E105.
Mur P, De Voer RM, Olivera-Salguero R, Rodríguez-Perales S, Pons T, Setién F, Aiza G, Valdés-Mas R, Bertini A, Pineda M, Vreede L, Navarro M, Iglesias S, González S, Brunet J, Valencia A, Esteller M, Lázaro C, Kops GJPL, Urioste M, Puente XS, Capellá G, Valle L (2018). Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis. Mol Can 17, 23.
Benítez-Burraco A, Barcos-Martínez M, Espejo-Portero I, Fernández-Urquiza M, Torres-Ruiz R, Rodríguez-Perales S, Jiménez-Romero MS (2018). Narrowing the genetic causes of language dysfunction in the 1q21.1 microduplication syndrome. Front Pediatr 6, 163.
Remacha L, Currás-Freixes M, Torres-Ruiz R, Schiavi F, Torres-Pérez R, Calsina B, Letón R, Comino-Méndez I, Roldán-Romero JM, Montero-Conde C, Santos M, Pérez LI, Pita G, Alonso MR, Honrado E, Pedrinaci S, Crespo-Facorro B, Percesepe A, Falcioni M, Rodríguez-Perales S, Korpershoek E, Ramón-Maiques S, Opocher G, Rodríguez-Antona C, Robledo M, Cascón A (2018). Gain-of-function mutations in DNMT3A in patients with paraganglioma. Genet Med 20, 1644-1651.
Rio-Machin A, Gómez-López G, Muñoz J, Garcia-Martinez F, Maiques-Diaz A, Alvarez S, Salgado RN, Shrestha M, Torres-Ruiz R, Haferlach C, Larráyoz MJ, Calasanz MJ, Fitzgibbon J, Cigudosa JC (2017). The molecular pathogenesis of the NUP98-HOXA9 fusion protein in acute myeloid leukemia.. Leukemia 31, 2000-2005.
Torres-Ruiz R, Rodriguez-Perales S, Bueno C, Menendez P. (2017). Modeling mixed-lineage-rearranged leukemia initiation in CD34+ cells: a “CRISPR” solution.. Haematologica 102, 1467-168.
Diez B, Genovese P, Roman-Rodriguez FJ, Alvarez L, Schiroli G, Ugalde L, Rodriguez-Perales S, Sevilla J, Diaz de Heredia C, Holmes MC, Lombardo A, Naldini L, Bueren JA, Rio P (2017). Therapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patients.. EMBO Mol Med 9, 1574-1588.
Torres-Ruiz R, Martinez-Lage M, Martin MC, Garcia A, Bueno C, Castaño J, Ramirez JC, Menendez P, Cigudosa JC, Rodriguez-Perales S (2017). Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9. Stem Cell Reports 8, 1408-1420.
Castaño J, Bueno C, Jiménez-Delgado S, Roca-Ho H, Fraga MF, Fernandez AF, Nakanishi M, Torres-Ruiz R, Rodríguez-Perales S, Menéndez P (2017). Generation and characterization of a human iPSC cell line expressing inducible Cas9 in the “safe harbor” AAVS1 locus. Stem Cell Res 21, 137-140.
Torres-Ruiz R, Rodriguez-Perales S (2017). CRISPR-Cas9 technology: applications and human disease modelling.. Brief Funct Genomics 16, 4-12.
Martinez-Lage M, Torres-Ruiz R, Rodriguez-Perales S (2017). CRISPR/Cas9 Technology: Applications and Human Disease Modeling.. Prog Mol Biol Transl Sci 152, 23-48.
Richart L, Carrillo-de Santa Pau E, Rio-Machin A, Pérez de Andrés M, Cigudosa JC, Sanchez-Arevalo Lobo VJ, Real FX (2016). BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis.. Nat Communications 7, 10153.
Rodriguez-Perales S, Torres-Ruiz R, Suela J, Acquadro F, Martin MC, Yebra E, Ramirez JC, Alvarez S, Cigudosa JC (2016). Truncated RUNX1 protein generated by a novel t(1;21)(p32;q22) chromosomal translocation impairs the proliferation and differentiation of human hematopoietic progenitors.. Oncogene 35, 125-134.
Muñoz-López A, Romero-Moya D, Prieto C, Ramos-Mejía V, Agraz-Doblas A, Varela I, Buschbeck M, Palau A, Carvajal-Vergara X, Giorgetti A, Ford A, Lako M, Granada I, Ruiz-Xivillé N, Rodríguez-Perales S, Torres-Ruíz R, Stam RW, Fuster JL, Fraga MF, Nakanishi M, Cazzaniga G, Bardini M, Cobo I, Bayon GF, Fernandez AF, Bueno C, Menendez P (2016). Development refractoriness of MLL-rearranged human B cell acute leukemias to reprogramming into pluripotency.. Stem Cell Reports 7, 602-618.
Maiques-Diaz A, Hernando M, Sánchez-López A, Rio-Machin A, Shrestha M, Mulloy JC, Cigudosa JC, Alvarez S. (2016). MAPK8-mediated stabilization of SP1 is essential for RUNX1-RUNX1T1 – driven leukaemia.. Br J Haematol 172, 807-810.
Kamieniak MM, Rico D, Milne RL, Muñoz-Repeto I, Ibáñez K, Grillo MA, Domingo S, Borrego S, Cazorla A, García-Bueno JM, Hernando S, García-Donas J, Hernández-Agudo E, Ramón y Cajal T, Robles-Díaz L, Márquez-Rodas I, Cusidó M, Sáez R, Lacambra-Calvet C, Osorio A, Urioste M, Cigudosa JC, Paz-Ares L, Palacios J, Benítez J , García MJ (2015). Deletion At 6Q24.2-26 Predicts Longer Survival Of High-Grade Serous Epithelial Ovarian Cancer Patients.. Mol Oncol 9, 422-436.
Torres-Ruiz R, Rodriguez-Perales S (2015). CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling.. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 16, 22151-22168.
Menezes J, Cigudosa JC (2015). Chronic neutrophilic leukemia: a clinical perspective. Oncotargets and Therpay 8, 2383-2390.
Calvete O, Martinez P, Garcia-Pavia P, Benitez-Buelga C, Paumard-Hernández B, Fernandez V, Dominguez F, Salas C, Romero-Laorden N, Garcia-Donas J, Carrillo J, Perona R, Triviño JC, Andrés R, Cano JM, Rivera B, Alonso-Pulpon L, Setien F, Esteller M, Rodriguez-Perales S, Bougeard G, Frebourg T, Urioste M, Blasco MA, Benítez J. (2015). A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families.. Nat Communications 6, 8383.
Torres R, Martin MC, Garcia A, Cigudosa JC, Ramirez JC, Rodriguez-Perales S (2014). Engineering human tumour-associated chromosomal translocations with the RNA-guided CRISPR-Cas9 system.. Nat Communications 5, 3964.
Menezes J, Acquadro F, Wiseman M, Gómez-López G, Salgado RN, Talavera-Casañas JG, Buño I, Cervera JV, Montes-Moreno S, Hernández-Rivas JM, Ayala R, Calasanz MJ, Larrayoz MJ, Brichs LF, Gonzalez-Vicent M, Pisano DG, Piris MA, Alvarez S, Cigudosa JC. (2014). Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm.. Leukemia 28, 823-829.
Chambers JS, Tanaka T, Brend T, Ali H, Geisler NJ, Khazin L, Cigudosa JC, Dear TN, MacLennan K, Rabbitts TH (2014). Sequential gene targeting to make chimeric tumor models with de novo chromosomal abnormalities.. Cancer Res 74, 1588-1597.
Duarte B, Miselli F, Murillas R, Espinosa-Hevia L, Cigudosa JC, Recchia A, Del Río M, Larcher F (2014). Long-term skin regeneration from a gene-targeted human epidermal stem cell clone.. Mol Ther 22, 1878-1880.
Torres R, Garcia A, Jimenez M, Rodriguez S, Ramirez JC. (2014). An integration-defective lentivirus-based resource for site-specific targeting of an edited safe-harbour locus in the human genome.. Gene Ther 21, 343-352.
Salgado RN, Menezes J, Calvente M, Suela J, Acquadro F, Martínez-Laperche C, Flores R, Trujillo M, Alvarez S, Cigudosa JC (2014). Myeloid neoplasms with der(1)t(1;19) may constitute a specific entity characterized by a cytogenetic biomarker and gene mutations involved in DNA methylation.. Leuk Lymphoma 55, 2652-2655.
Balbás-Martínez C, Sagrera A, Carrillo-de-Santa-Pau E, Earl J, Márquez M, Vazquez M, Lapi E, Castro-Giner F, Beltran S, Bayés M, Carrato A, Cigudosa JC, Domínguez O, Gut M, Herranz J, Juanpere N, Kogevinas M, Langa X, López-Knowles E, Lorente JA, Lloreta J, Pisano DG, Richart L, Rico D, Salgado RN, Tardón A, Chanock S, Heath S, Valencia A, Losada A, Gut I, Malats N, Real FX (2013). Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.. Nat Genet 45, 1464-1469.
Rio-Machin A, Ferreira BI, Henry T, Gómez-López G, Agirre X, Alvarez S, Rodriguez-Perales S, Prosper F, Calasanz MJ, Martínez J, Fonseca R, Cigudosa JC (2013). Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype.. Leukemia 27, 925-931.
Gómez-Casares MT, García-Alegria E, López-Jorge CE, Ferrándiz N, Blanco R, Alvarez S, Vaqué JP, Bretones G, Caraballo JM, Sánchez-Bailón P, Delgado MD, Martín-Perez J, Cigudosa JC, León J (2013). MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1).. Oncogene 32, 2239-2246.
Odqvist L, Sánchez-Beato M, Montes-Moreno S, Martín-Sánchez E, Pajares R, Sánchez-Verde L, Ortiz-Romero PL, Rodriguez J, Rodríguez-Pinilla SM, Iniesta-Martínez F, Solera-Arroyo JC, Ramos-Asensio R, Flores T, Palanca JM, Bragado FG, Franjo PD, Piris MA. (2013). NIK Controls Classical and Alternative NF-?B Activation and Is Necessary for the Survival of Human T-cell Lymphoma Cells.. Clin Cancer Res 19, 2319-2330.
Pérez C, Pascual M, Martín-Subero JI, Bellosillo B, Segura V, Delabesse E, Álvarez S, Larrayoz MJ, Rifón J, Cigudosa JC, Besses C, Calasanz MJ, Cross NC, Prósper F, Agirre X. (2013). Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms.. Haematologica 98, 1414-1420.
Pros E, Lantuejoul S, Sanchez-Verde L, Castillo SD, Bonastre E, Suarez-Gauthier A, Conde E, Cigudosa JC, Lopez-Rios F, Torres-Lanzas J, Castellví J, Ramon y Cajal S, Brambilla E, Sanchez-Cespedes M. (2013). Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer.. Int J Cancer 133, 898-907.
Mallo M, Del Rey M, Ibáñez M, Calasanz MJ, Arenillas L, Larráyoz MJ, Pedro C, Jerez A, Maciejewski J, Costa D, Nomdedeu M, Diez-Campelo M, Lumbreras E, González-Martínez T, Marugán I, Such E, Cervera J, Cigudosa JC, Alvarez S, Florensa L, Hernández JM, Solé F (2013). Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.. Br J Haematol 162, 74-86.
Montesinos-Rongen M, Sánchez-Ruiz M, Brunn A, Hong K, Bens S, Perales SR, Cigudosa JC, Siebert R, Deckert M (2013). Mechanisms of intracerebral lymphoma growth delineated in a syngeneic mouse model of central nervous system lymphoma.. J Neuropath Exp Neur 72, 325-336.
Chamorro C, Almarza D, Duarte B, Llames SG, Murillas R, García M, Cigudosa JC, Espinosa-Hevia L, Escámez MJ, Mencía A, Meana A, García-Escudero R, Moro R, Conti CJ, Del Río M, Larcher F (2013). Keratinocyte cell lines derived from severe generalized recessive Epidermolysis Bullosa patients carrying a highly recurrent COL7A1 homozygous mutation: models to assess cell and gene therapies in vitro and in vivo.. Exp Dermatol 22, 601-603.
López V, González-Peramato P, Suela J, Serrano A, Algaba F, Cigudosa JC, Vidal A, Bellmunt J, Heredero O, Sánchez-Carbayo M (2013). Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA.. J Transl Med 11, 182.
Menezes J, Makishima H, Gomez I, Acquadro F, Gómez-López G, Graña O, Dopazo A, Alvarez S, Trujillo M, Pisano DG, Maciejewski JP, Cigudosa JC (2013). CSF3R T618I co-occurs with mutations of splicing and epigenetic genes and with a new PIM3 truncated fusion gene in chronic neutrophilic leukemia.. Blood Cancer J 3, e158.
Menezes J, Salgado RN, Acquadro F, Gómez-López G, Carralero MC, Barroso A, Mercadillo F, Espinosa-Hevia L, Talavera-Casañas JG, Pisano DG, Alvarez S, Cigudosa JC (2013). ASXL1, TP53 and IKZF3 mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia.. Blood Cancer J 3, e157.