VHIO
Oncogenetics Group
Orland Díez
Staff Scientist
Sara Gutiérrez
Post Doctoral Fellow
Sandra Bonache
Technicians
Miriam Masas, Anna Tenés
PhD Student
Gemma Montalban
SUMMARY
Our work focuses on two main lines of research: 1) genetic predisposition to hereditary breast/ovarian cancer, and 2) genetic predisposition to radiotherapy-induced toxicity. This year we have performed exome sequence analysis of affected relatives from breast cancer families negative for BRCA1/2 pathogenic variants in order to unmask new potential predisposing genes, as well as developed a panel of around one hundred predisposition cancer genes by massive sequencing.
We have led a multicenter study to determine the prevalence of RAD51D disease-causing variants in Spanish breast/ovarian cancer families, and described the evaluation of methodologies for DNA/RNA analysis, and alternative transcripts in BRCA1 and BRCA2 genes, collaborating with the working groups of the Evidence Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) International Consortium. We have also participated in the Investigators of Modifiers of BRCA1/2 (CIMBA) Consortium. This collective partnership has since identified new susceptibility genes of ovarian cancer and modifier alleles for BRCA1/BRCA2 mutation carriers.
Our group has shown that severe, late side effects induced by radiotherapy of breast cancer are associated with low levels of irradiation-induced apoptosis. Aimed at validating predictive models of radiotherapy toxicity to improve quality-of-life and reduce side-effects in cancer survivors, we have also enrolled breast cancer patients to collaborate in the European Commission FP7-funded project REQUITE.
PUBLICATIONS
- Ruiz de Garibay G, Acedo A, García-Casado Z, Gutiérrez-Enríquez S, Tosar A, Romero A, Garre P, Llort G, Thomassen M, Díez O, Pérez-Segura P, Díaz-Rubio E, Velasco EA, Caldés T, de la Hoya M. Capillary Electrophoresis Analysis of Conventional Splicing Assays: IARC Analytical and Clinical Classification of 31 BRCA2 Genetic Variants. Hum Mutat2014; 35:53-7. IF: 5,122.
- Gutiérrez-Enríquez S, Bonache S, Ruíz de Garibay G, Osorio A, Santamariña M, Ramón Y Cajal T, Esteban-Cardeñosa E, Tenés A, Yanowsky K, Barroso A, Montalban G, Blanco A, Cornet M, Gadea N, Infante M, Caldés T, Díaz-Rubio E, Balmaña J, Lasa A, Vega A, Benítez J, de la Hoya M, Diez O. About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants. Int J Cancer 2014; 134:2088-97. IF: 5,007.
- Whiley P, de la Hoya M, Thomassen M, Becker A, Brandão R, Pedersen IS, Montagna M, Menéndez M, Quiles F, Enríquez SG, De Leeneer K, Tenés A, Montalban G, Tserpelis D, Yoshimatsu T, Tirapo C, Raponi M, Caldes T, Blanco A, Santamariña M, Guidugli L, de Garibay GR, Wong M, Tancredi M, Fachal L, Ding Y, Kruse T, Lattimore V, Kwong A, Chan T, Colombo M, De Vecchi G, Caligo M, Baralle D, Lázaro C, Couch F, Radice P, Southey M, Neuhausen S, Houdayer C, Fackenthal J, Hansen T, Vega A, Diez O, Blok R, Claes K, Wappenschmidt B, Walker L, Spurdle A, Brown M; on behalf of the ENIGMA consortium. Comparison of mRNA Splicing Assay Protocols across Multiple Laboratories: Recommendations for Best Practice in Standardized Clinical Testing. Clin Chem2014; 60:341-52. IF: 7,768.
- Colombo M, Blok MJ, Whiley P, Santamariña M, Gutiérrez-Enríquez S, Romero A, Garre P, Becker A, Smith LD, De Vecchi G, Brandão RD, Tserpelis D, Brown M, Blanco A, Bonache S, Menéndez M, Houdayer C, Foglia C, Fackenthal JD, Baralle D, Wappenschmidt B; kConFaB, Díaz-Rubio E, Caldés T, Walker L, Díez O, Vega A, Spurdle AB, Radice P, de la Hoya M. Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: a report from the ENIGMA consortium. Hum Mol Genet 2014; 23:3666-80. IF: 6,677.
- Rosenstein BS, West CM, Bentzen SM, Alsner J, Andreassen CN, Azria D, Barnett GC, Baumann M, Burnet N, Chang-Claude J, Chuang EY, Coles CE, Dekker A, De Ruyck K, De Ruysscher D, Drumea K, Dunning AM, Easton D, Eeles R, Fachal L, Gutiérrez-Enríquez S, Haustermans K, Henríquez-Hernández LA, Imai T, Jones GD, Kerns SL, Liao Z, Onel K, Ostrer H, Parliament M, Pharoah PD, Rebbeck TR, Talbot CJ, Thierens H, Vega A, Witte JS, Wong P, Zenhausern F; Radiogenomics Consortium. Radiogenomics: radiobiology enters the era of big data and team science. Int J Radiat Oncol Biol Phys 2014; 89:709-13. IF: 4,176.
MAIN RESEARCH PROJECTS
View- Análisis del exoma mediante secuenciación masiva para la identificación de nuevos genes de susceptibilidad al cáncer de mama.
Instituto de Salud Carlos III
PrincipaI Investigator: Sara Gutiérrez Enríquez - Aplicación de la secuenciación masiva para la optimización del diagnóstico molecular del cáncer de mama y ovario hereditario.
Instituto de Salud Carlos III
Principal Investigator: Orland Díez - Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality-of-life in cancer survivors-REQUITE” (Nº: 601826).
European Commission FP7
Local Principal Investigator: Sara Gutiérrez Enríquez - Optimización del diagnóstico molecular del cáncer de mama y ovario hereditario: estudio de las variantes genéticas de efecto clínico desconocido en BRCA1 y BRCA2 mediante análisis funcionales y de transcripción y desarrollo de un nuevo predictor in silico.
Instituto de Salud Carlos III
Principal Investigator: Sara Gutiérrez Enríquez