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
Marta Martínez-Lage
Francisco José Moya

Recurrent chromosomal rearrangements − changes in the structure of native chromosomes − are very common and wellknown hallmarks of cancer. Recent technological advances have improved our ability to detect and understand these rearrangements. A better understanding of these cancercausing mechanisms will lead to novel therapeutic regimens to fight cancer. The research activity of the Molecular Cytogenetics and Genome Editing Unit focuses on increasing the knowledge about the role of chromosomal rearrangements in cancer development and progression and the discovery of new therapeutic targets. With the combined use of CRISPR genome editing and cytogenetic technologies, we are creating 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 engineering. The Unit is continuously implementing and developing new technologies in those fields. We also participate in collaborative projects with clinical and basic science investigators at the CNIO and other institutions.

Publications

Petazzi P, Torres-Ruiz R, Fidanza A, Roca-Ho H, Gutierrez-Agüera F, Castaño J, Rodriguez-Perales S, Díaz de la Guardia R, López-Millán B, Bigas A, Forrester LM, Bueno C, Menéndez P (2020). Robustness of Catalytically Dead Cas9 Activators in Human Pluripotent and Mesenchymal Stem Cells.. Molecular Therapy-Nucleic Acids 20, 196-204. CNIO Publication. Open Access
Martinez-Lage M, Torres-Ruiz R, Puig-Serra P, Moreno-Gaona P, Martin MC, Moya FJ, Quintana-Bustamante O, Garcia-Silva S, Carcaboso AM, Petazzi P, Bueno C, Mora J, Peinado H, Segovia JC, Menendez P, Rodriguez-Perales S (2020). In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Nat Commun (in press). CNIO Publication.
Redondo-Antón J, Fontela MG, Notario L, Torres-Ruiz R, Rodríguez-Perales S, Lorente E, Lauzurica P (2020). Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression. Front Genet 11, 552949. CNIO Publication.
Torres-Gomez A, Sanchez-Trincado JL, Toribio V, Torres-Ruiz R, Rodríguez-Perales S, Yáñez-Mó M, Reche PA, Cabañas C, Lafuente EM (2020). RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment. Cells (in press). CNIO Publication.
Molina O, Vinyoles M, Granada I, Roca-Ho H, Gutierrez-Agüera F, Valledor L, López-López CM, Rodríguez-González P, Trincado JL, Tirados-Menéndez S, Pal D, Ballerini P, Den Boer ML, Plensa I, Perez-Iribarne MDM, Rodriguez-Perales S, Calasanz MJ, Ramírez M, Rodríguez R, Camos M, Calvo M, Bueno C, Menendez P (2020). Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL.. Blood 136, 313-327. CNIO Publication.
Pino-Barrio MJ, Giménez Y, Villanueva M, Hildenbeutel M, Sánchez-Dominguez R, Rodríguez-Perales S, Pujol R, Surrallés J, Río P, Cathomen T, Mussolino C, Bueren JA, Navarro S (2020). TALEN mediated gene editing in a mouse model of Fanconi anemia.. Sci Rep 10, 6997. CNIO Publication. Open Access
Khoshchehreh R, Totonchi M, Carlos Ramirez J, Torres R, Baharvand H, Aicher A, Ebrahimi M, Heeschen C (2019). Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity.. Oncogene 38, 6226-6239. CNIO Publication.
Quintana-Bustamante O, Fañanas-Baquero S, Orman I, Torres R, Duchateau P, Poirot L, Gouble A, Bueren JA, Segovia JC (2019). Gene editing of PKLR gene in human hematopoietic progenitors through 5′ and 3′ UTR modified TALEN mRNA. PLoS One 14, e0223775. CNIO Publication. Open Access
Román-Rodríguez FJ, Ugalde L, Álvarez L, Díez B, Ramírez MJ, Risueño C, Cortón M, Bogliolo M, Bernal S, March F, Ayuso C, Hanenberg H, Sevilla J, Rodríguez-Perales S, Torres-Ruiz R, Surrallés J, Bueren JA, Río P (2019). NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia. Cell Stem Cell 25, 607-621. CNIO Publication.
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. CNIO Publication.
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). CNIO Publication.
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. CNIO Publication. Open Access
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 27, 986-998. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
Torres-Ruiz R, Rodriguez-Perales S (2017). CRISPR-Cas9 technology: applications and human disease modelling.. Brief Funct Genomics 16, 4-12. CNIO Publication.
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. CNIO Publication.
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 Commun 7, 10153. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
Torres-Ruiz R, Rodriguez-Perales S (2015). CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling.. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 16, 22151-22168. CNIO Publication.
Menezes J, Cigudosa JC (2015). Chronic neutrophilic leukemia: a clinical perspective. Oncotargets and Therpay 8, 2383-2390. CNIO Publication.
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 Commun 6, 8383. CNIO Publication. Open Access