Molecular Cytogenetics Unit

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

Staff Scientists

Raúl Torres

Graduate Students

Alejandro Alonso
Alejandro Nieto
Pilar Puig

Technicians

M. Carmen Martín
Francisco José Moya

Recurrent chromosomal rearrangements – changes in the structure of native chromosomes – are very common and well-known hallmarks of cancer. A better understanding of these cancer-causing 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 discovering new therapeutic targets. With the combined use of CRISPR genome editing and cytogenetic technologies, we are creating models that recapitulate chromosomal and genetic cancer alterations. The goal of the Unit is to provide CNIO and external researchers with the latest technologies used in the fields of molecular cytogenetics and genome editing. The Unit is continuously implementing and developing new technologies in those fields. We also participate in collaborative projects with clinical and basic science investigators across the CNIO and other institutions.

Publications

Montero-Conde C, Leandro-García LJ, Martínez-Montes ÁM, Martínez P, Moya FJ, Letón R, Gil E, Martínez-Puente N, Guadalix S, Currás-Freixes M, García-Tobar L, Zafon C, Jordà M, Riesco-Eizaguirre G, González-García P, Monteagudo M, Torres-Pérez R, Mancikova V, Ruiz-Llorente S, Pérez-Martínez M, Pita G, Galofré JC, Gonzalez-Neira A, Cascón A, Rodríguez-Antona C, Megías D, Blasco MA, Caleiras E, Rodríguez-Perales S, Robledo M (2022). Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers. Clin Transl Med 12, e1001. CNIO Publication.
Zanetti SR, Velasco-Hernandez T, Gutierrez-Agüera F, Díaz VM, Romecín PA, Roca-Ho H, Sánchez-Martínez D, Tirado N, Baroni ML, Petazzi P, Torres-Ruiz R, Molina O, Bataller A, Fuster JL, Ballerini P, Juan M, Jeremias I, Bueno C, Menéndez P (2022). A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL.. Mol Ther 30, 550-563. CNIO Publication.
Rodriguez-Cortez VC, Navarrete-Meneses MP, Molina O, Velasco-Hernandez T, Gonzalez J, Romecin P, Gutierrez-Aguera F, Roca-Ho H, Vinyoles M, Kowarz E, Marin P, Rodriguez-Perales S, Gomez-Marin C, Perez-Vera P, Cortes-Ledesma F, Bigas A, Terron A, Bueno C, Menendez P. (2022). The insecticides permethrin and chlorpyrifos show limited genotoxicity and no leukemogenic potential in human and murine hematopoietic stem progenitor cells. Haematologica 107, 544-549. CNIO Publication.
Puig-Serra P, Casado-Rosas MC, Martinez-Lage M, Olalla-Sastre B, Alonso-Yanez A, Torres-Ruiz R, Rodriguez-Perales S (2022). CRISPR Approaches for the Diagnosis of Human Diseases.. Int J Mol Sci 23, 1757. CNIO Publication.
Álvarez EG, Demeulemeester J, Otero P, Jolly C, García-Souto D, Pequeño-Valtierra A, Zamora J, Tojo M, Temes J, Baez-Ortega A, Rodriguez-Martin B, Oitaben A, Bruzos AL, Martínez-Fernández M, Haase K, Zumalave S, Abal R, Rodríguez-Castro J, Rodriguez-Casanova A, Diaz-Lagares A, Li Y, Raine KM, Butler AP, Otero I, Ono A, Aikata H, Chayama K, Ueno M, Hayami S, Yamaue H, Maejima K, Blanco MG, Forns X, Rivas C, Ruiz-Bañobre J, Pérez-Del-Pulgar S, Torres-Ruiz R, Rodriguez-Perales S, Garaigorta U, Campbell PJ, Nakagawa H, Van Loo P, Tubio JMC. (2021). Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture. Nat Commun 12, 6910. CNIO Publication.
Tejedor JR, Bueno C, Vinyoles M, Petazzi P, Agraz-Doblas A, Cobo I, Torres-Ruiz R, Bayón GF, Pérez RF, López-Tamargo S, Gutierrez-Agüera F, Santamarina-Ojeda P, Ramírez-Orellana M, Bardini M, Cazzaniga G, Ballerini P, Schneider P, Stam RW, Varela I, Fraga MF, Fernández AF, Menéndez P (2021). Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLL-rearranged B cell acute lymphoblastic leukemia. J Clin Invest 131, e138833. CNIO Publication.
Castro-Sánchez P, Hernández-Pérez S, Aguilar-Sopeña O, Ramírez-Muñoz R, Rodríguez-Perales S, Torres-Ruiz R, Roda-Navarro P (2021). Fast diffusion sustains plasma membrane accumulation of phosphatase of regenerating liver-1.. Front Cell Dev Biol 8, 585842. CNIO Publication.
Monteagudo M, Martínez P, Leandro-García LJ, Martínez-Montes ÁM, Calsina B, Pulgarín-Alfaro M, Díaz-Talavera A, Mellid S, Letón R, Gil E, Pérez-Martínez M, Megías D, Torres-Ruiz R, Rodriguez-Perales S, González P, Caleiras E, Jiménez-Villa S, Roncador G, Álvarez-Escolá C, Regojo RM, Calatayud M, Guadalix S, Currás-Freixes M, Rapizzi E, Canu L, Nölting S, Remde H, Fassnacht M, Bechmann N, Eisenhofer G, Mannelli M, Beuschlein F, Quinkler M, Rodríguez-Antona C, Cascón A, Blasco MA, Montero-Conde C, Robledo M (2021). Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma. Cancers 13, 4758. CNIO Publication.
Baquero JM, Benítez-Buelga C, Rajagopal V, Zhenjun Z, Torres-Ruiz R, Müller S, Hanna BMF, Loseva O, Wallner O, Michel M, Rodríguez-Perales S, Gad H, Visnes T, Helleday T, Benítez J, Osorio A. (2021). Small molecule inhibitor of OGG1 blocks oxidative DNA damage repair at telomeres and potentiates methotrexate anticancer effects. Sci Rep 11, 3490. CNIO Publication.
Manso R, Rodríguez-Perales S, Torres-Ruiz R, Santonja C, Rodríguez-Pinilla SM. (2021). PD-L1 expression in peripheral T-cell lymphomas is not related to either PD-L1 gene amplification or rearrangements. Leuk Lymphoma 62, 1648-1656. CNIO Publication.
Calvete O, Reyes J, Valdés-Socin H, Martin P, Marazuela M, Barroso A, Escalada J, Castells A, Torres-Ruiz R, Rodríguez-Perales S, Currás-Freixes M, Benítez J. (2021). Alterations in SLC4A2, SLC26A7 and SLC26A9 Drive Acid-Base Imbalance in Gastric Neuroendocrine Tumors and Uncover a Novel Mechanism for a Co-Occurring Polyautoimmune Scenario. Cells 10, 3500. CNIO Publication.
García-Silva S, Benito-Martín A, Nogués L, Hernández-Barranco A, Mazariegos MS, Santos V, Hergueta-Redondo M, Ximénez-Embún P, Kataru RP, Lopez AA, Merino C, Sánchez-Redondo S, Graña-Castro O, Matei I, Nicolás-Avila JÁ, Torres-Ruiz R, Rodríguez-Perales S, Martínez L, Pérez-Martínez M, Mata G, Szumera-Cieckiewicz A, Kalinowska I, Saltari A, Martínez-Gómez JM, Hogan SA, Saragovi HU, Ortega S, Garcia-Martin C, Boskovic J, Levesque MP, Rutkowski P, Hidalgo A, Muñoz J, Megías D, Mehrara BJ, Lyden D, Peinado H (2021). Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nat Cancer 2, 1387-1405. CNIO Publication.
Torres-Ruiz R, Grazioso TP, Brandt M, Martinez-Lage M, Rodriguez-Perales S, Djouder N. (2021). Detection of chromosome instability by interphase FISH in mouse and human tissues. Star Protocols 2, 100631. 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.
Visnes T, Benítez-Buelga C, Cázares-Körner A, Sanjiv K, Hanna BMF, Mortusewicz O, Rajagopal V, Albers JJ, Hagey DW, Bekkhus T, Eshtad S, Baquero JM, Masuyer G, Wallner O, Müller S, Pham T, Göktürk C, Rasti A, Suman S, Torres-Ruiz R, Sarno A, Wiita E, Homan EJ, Karsten S, Marimuthu K, Michel M, Koolmeister T, Scobie M, Loseva O, Almlöf I, Unterlass JE, Pettke A, Boström J, Pandey M, Gad H, Herr P, Jemth AS, El Andaloussi S, Kalderén C, Rodriguez-Perales S, Benítez J, Krokan HE, Altun M, Stenmark P, Berglund UW, Helleday T (2020). Targeting OGG1 arrests cancer cell proliferation by inducing replication stress.. Nucleic Acids Res 48, 12234-12251. 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 11, 5060. CNIO Publication. Open Access
Oldrini B, Vaquero-Siguero N, Mu Q, Kroon P, Zhang Y, Galán-Ganga M, Bao Z, Wang Z, Liu H, Sa JK, Zhao J, Kim H, Rodriguez-Perales S, Nam DH, Verhaak RGW, Rabadan R, Jiang T, Wang J, Squatrito M (2020). MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nat Commun 11, 3833. CNIO Publication. Open Access
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
Castro-Sánchez P, Hernández-Pérez S, Aguilar-Sopeña O, Ramírez-Muñoz R, Rodríguez-Perales S, Torres-Ruiz R, Roda-Navarro P (2020). Fast diffusion sustains plasma membrane accumulation of phosphatase of regenerating liver-1.. Front Cell Dev Biol 8, 585842. 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
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 9, 1166. 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.
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.
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.
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.
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.
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
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
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
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
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.
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
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
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
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.
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.
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.
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.