CFAH CANCER GENOMICS GROUP – VHIO – Vall d'Hebron Institute of Oncology

CANCER GENOMICS GROUP

CORE TECHNOLOGIES
Cancer Genomics Group

ANA VIVANCOS
Principal Investigator
Biosketch

 

VHIO’s Cancer Genomics Group serves as a Core Technology laboratory. In addition, we are dedicated to translational research as well as novel genomic test development.

We provide cutting-edge applications in cancer genomics through state-of-the-art technologies and the development of novel, fully validated tests that are used in the clinical research setting (Prescreening Program). Our lab is equipped with an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD) and two NextGen Sequencers; MiSeq and HiSeq2500, Illumina.

VHIO’s Prescreening Program, is nucleated around the activity of two VHIO groups – Cancer Genomics and Molecular Oncology, led by Paolo Nuciforo, in collaboration with VHIO’s Elena Garralda (PI of our Early Clinical Drug Development Group), and Rodrigo Dienstmann (PI, Oncology Data Science – ODysSey – Group, and centers on performing molecular profiling in over 1500 patients each year as potential candidates for enrollment in our Phase I clinical trials led by VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Elena Garralda.

Patients’ suitability for inclusion in any given clinical trial is assessed based on their respective genomic or pathologic profile. Our Group has developed and routinely implemented several tests for our Prescreening Program. Two are based on NGS: an Amplicon-seq approach to sequence 67 genes as well as a 450-gene capture panel (Illumina). This panel is currently being validated.

Another two are based on nCounter (Nanostring). The gene fusion panel, with the capacity of detecting over 100 recurrent gene fusions, is also enabling us to assess gene expression patterns in tumors. Copy Number Alterations are evaluated with a 59 gene panel for genes with frequent gains or losses in cancer.

As a reflection of our dedication to excellence and quality in the services we provide, we have attained ISO 15189 flexible accreditation for our Amplicon-seq testing method.

Our research activities focus on developing novel multiplexed tests that are optimized to FFPE-derived nucleic acids. Once developed, they are validated and used in clinical and translational research.

We are involved in a number of translational research projects including the identification of mechanisms of resistance to targeted therapies, as well as predictive biomarkers for immunotherapeutics. Our group is particularly interested in liquid biopsy; ctDNA as well as tumor educated platelets (TEPs).

 

STRATEGIC GOALS

  • Develop and implement improved strategies for routine patient prescreening in a setting of excellence (ISO 15189 flexible accreditation).
  • Provide cutting-edge applications in cancer genomics through the use of novel technologies and protocol development.
  • Prioritize translational projects and partnerships that reinforce VHIO’s renowned excellence in oncology, such as those we are currently pursuing with our Thoracic Tumors Group, led by Enriqueta Felip, and Gastrointestinal & Endocrine Tumors Group, directed by Josep Tabernero.

HIGHLIGHTS

  • VHIO is one of the six founding partners of the Cancer Core Europe Consortium alongside the Gustave Roussy Cancer Campus Grand Paris (Villejuif, France), Cambridge Cancer Centre (Cambridge, UK), Karolinska Institute (Stockholm, Sweden), Netherlands Cancer Institute – NKI (Amsterdam, The Netherlands), and the National Center for Tumor Diseases–DKFZ-NCT (Heidelberg, Germany), and, most recently incorporating the National Cancer Institute of Milan (INT). Our group is appointed co-leader of the Consortium’s Genomics Taskforce and is responsible for the alignment of genomic testing across all member institutions.
  • We are now validating our 450 gene capture panel to be used in our Prescreening Program and by all Cancer Core Europe Consortium partners.
  • In liquid biopsy we are developing our custom NGS test with Unique Molecular Identifiers (UMI) chemistry and envision that this will be our first disease tracking test in the clinical setting.
  • VHIO is one of the few centers in Europe to run such a comprehensive prescreening program. Molecular profiling in around 1500 patients per year as candidates for enrollment in our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, early clinical trials enables our teams to more precisely match an increasing number of individual patients with a particular study.

PROJECTS

  • Avanzando hacia la implementación clínica: Estudio de las bases moleculares de la liberación de DNA tumoral en sangre. FIS-ISCIII.  (PI20/01112).
    PI: Ana Vivancos.
    01/01/2021 – 31/12/2023.
  • Validation of BRCA1/2 mutation detection in Tissue and Germline. AstraZéneca.
    PI: Ana Vivancos.
    02/05/2020 – 31/12/2020.
  • ctDNA in breast milk for early detection of pregnancy associated breast cancer. FERO.
    PI: Ana Vivancos.
    01/07/2020 – 30/06/2022.
  • Tumores primarios múltiples en pacientes con cáncer de pulmón: elaboración de un perfil molecular integral para elucidar orígenes genéticos comunes.
    Fundación Científica de la Asociación Española Contra el Cáncer (AECC).
    PI: Ana Vivancos.
    01/12/2019 – 30/11/2023.
  • Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesophageal Junction cancer (GECJ).
    Merck Healthcare KGaA.
    PI: Ana Vivancos.
    10/04/2019 – 31/12/2026.
  • Measuring NRG1 mRNA levels by means of Nanostring at Vall d’Hebron.
    MERUS, NV.
    PI: Ana Vivancos.
    30/04/2019 – 31/12/2020.
  • Biomarker testing NSG analysis.
    Puma Biotechnology, Inc.
    PI:  Ana Vivancos.
    01/01/2019 – 30/09/2020
  • CeLac and European consortium for a personalized medicine approach to Gastric Cancer-LEGACy.
    European Commission-LEGACy.
    PI: Ana Vivancos.
    01/01/2019-31/12/2022.
  • Moving liquid biopsy beyond current applications: study of prognostic and predictive values of circulating. Spanish Association against Cancer (AECC) PI: Ana Vivancos 2018 – 2021

TEAM

  • Principal Investigator
    • Ana Vivancos
  • Post-Doctoral Fellows
    • Alberto Gonzalez
    • Miriam Sansó
  • Specialized Technicians
    • Ginevra Caratú
    • Deborah G. Lo Giacco
    • Agatha Martin
    • Judit Matito
    • Miriam Navarro
    • Zighereda Ogbah
    • Laia Ramos
  • Bioinformatician
    • Francesco M. Mancuso
  • Bioinformatician Aux. Tec.
    • Marina Gómez
    • Laura Muiños

 


Most relevant scientific publications

  • Capdevila J, Mayor R, Mancuso FM, Iglesias C, Caratú G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Álvarez CV, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J. Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol. 2019 Nov 1;30(11):1843.
  • Vivancos A, Élez E, Salazar R. Circulating cell-free DNA as predictor of treatment failure after neoadjuvant chemoradiotherapy before surgery in patients with locally advanced rectal cancer: is it ready for primetime? Ann Oncol.29: 532-534.
  • Capdevila J,Mayor R; Mancuso FF, Iglesias C; Caratù G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Álvarez C, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J. Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol.29: 1454-1460.
  • Cedrés S, Felip E, Cruz C, Martinez de Castro A, Pardo N, Navarro A, Martinez-Marti A, Remon J, Zeron-Medina J, Balmaña J, Llop-Guevara A, Miquel JM, Sansano I, Nuciforo P,Mancuso F, Serra V, Vivancos A. Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation. J Natl Cancer Inst.110: 914-917.
  • Puig I, Tenbaum SP, Chicote I, Arqués O,Martínez-Quintanilla J, Cuesta-Borrás E, Ramírez L, Gonzalo P, Soto A, Aguilar S, Eguizabal C, Caratù G, Prat A, Argilés G, Landolfi S, Casanovas O, Serra V, Villanueva A, Arroyo AG, Terracciano L, Nuciforo P,Seoane J,Recio JA, Vivancos A,Dienstmann R,Tabernero J,Palmer HG.TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence. J Clin Invest.128: 3887-3905.
  • Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S,Llop-Guevara A, Ibrahim YH, Gris-Oliver A, Bonache S, Morancho B, Bruna A, Rueda OM, Lai Z, Polanska UM, Jones GN; Kristel P, de Bustos L, Guzman M,Rodriguez O, Grueso J, Montalban G, Caratú G,Mancuso F, Fasani R, Jiménez J, Howat WJ, Dougherty B, Vivancos A, Nuciforo P, Serres-Créixams X, Rubio IT, Oaknin A, Cadogan E, Barrett JC, Caldas C, Baselga J, Saura C, Cortés J, Arribas J, Jonkers J, Díez O; O’Connor MJ, Balmaña J,Serra V. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol.29: 1203-1210. IF: 13,926
  • Martínez-Ricarte F, Mayor R, Martínez-Sáez E, Rubio-Pérez C, Pineda E, Cordero E, Cicuéndez M, Poca MA, Lopez-Bigas N, Ramón Y Cajal S, Vieito M, Carles J, Tabernero J,Vivancos A, Gallego S, Graus F, Sahuquillo J, Seoane J. Molecular Diagnosis of Diffuse Gliomas through Sequencing of Cell-Free Circulating Tumor DNA from Cerebrospinal Fluid.Clin Cancer Res.24: 2812-2819.

All publications

  • Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer. Serna G, Ruiz-Pace F, Cecchi F, Fasani R, Jimenez J, Thyparambil S, Landolfi S, Elez E, Vivancos A, Hembrough T, Tabernero J, Dienstmann R, Nuciforo P. Sci Rep. 2019 Sep 19;9(1):13568.
  • Early evolutionary divergence between papillary and anaplastic thyroid cancers. Capdevila J, Mayor R, Mancuso FM, Iglesias C, Caratú G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Álvarez CV, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J. Ann Oncol. 2019 Nov 1;30(11):1843.
  • Impact of circulating tumor DNA mutant allele fraction on prognosis in RAS-mutant metastatic colorectal cancer.Elez E, Chianese C, Sanz-García E, Martinelli E, Noguerido A, Mancuso FM, Caratù G, Matito J, Grasselli J, Cardone C, Esposito Abate R, Martini G, Santos C, Macarulla T, Argilés G, Capdevila J, Garcia A, Mulet N, Maiello E, Normanno N, Jones F, Tabernero J, Ciardello F, Salazar R, Vivancos A. Mol Oncol. 2019 Sep;13(9):1827-1835.
  • Comparison of the Clinical Sensitivity of the Idylla Platform and the OncoBEAM RAS CRC Assay for KRAS Mutation Detection in Liquid Biopsy Samples. Vivancos A, Aranda E, Benavides M, Élez E, Gómez-España MA, Toledano M, Alvarez M, Parrado MRC, García-Barberán V, Diaz-Rubio E. Sci Rep. 2019 Jun 20;9(1):8976.
  • Genomic heterogeneity and efficacy of PI3K pathway inhibitors in patients with gynaecological cancer. Rodriguez-Freixinos V, Ruiz-Pace F, Fariñas-Madrid L, Garrido-Castro AC, Villacampa G, Nuciforo P, Vivancos A, Dienstmann R, Oaknin A. ESMO Open. 2019 Mar 8;4(2):e000444.
  • Vivancos A, Élez E, Salazar R. Circulating cell-free DNA as predictor of treatment failure after neoadjuvant chemoradiotherapy before surgery in patients with locally advanced rectal cancer: is it ready for primetime? Ann Oncol.29: 532-534.
  • Capdevila J, Mayor R; Mancuso FF, Iglesias C; Caratù G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Álvarez C, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J. Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol.29: 1454-1460.
  • Cedrés S, Felip E, Cruz C, Martinez de Castro A, Pardo N, Navarro A, Martinez-Marti A, Remon J, Zeron-Medina J, Balmaña J, Llop-Guevara A, Miquel JM, Sansano I, Nuciforo P, Mancuso F, Serra V, Vivancos A. Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation. J Natl Cancer Inst. 110: 914-917.
  • Puig I, Tenbaum SP, Chicote I, Arqués O, Martínez-Quintanilla J, Cuesta-Borrás E, Ramírez L, Gonzalo P, Soto A, Aguilar S, Eguizabal C, Caratù G, Prat A, Argilés G, Landolfi S, Casanovas O, Serra V, Villanueva A, Arroyo AG, Terracciano L, Nuciforo P, Seoane J, Recio JA, Vivancos A, Dienstmann R, Tabernero J, Palmer HG. TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence. J Clin Invest. 128: 3887-3905.
  • Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, Llop-Guevara A, Ibrahim YH, Gris-Oliver A, Bonache S, Morancho B, Bruna A, Rueda OM, Lai Z, Polanska UM, Jones GN; Kristel P, de Bustos L, Guzman M, Rodriguez O, Grueso J, Montalban G, Caratú G, Mancuso F, Fasani R, Jiménez J, Howat WJ, Dougherty B, Vivancos A, Nuciforo P, Serres-Créixams X, Rubio IT, Oaknin A, Cadogan E, Barrett JC, Caldas C, Baselga J, Saura C, Cortés J, Arribas J, Jonkers J, Díez O; O’Connor MJ, Balmaña J, Serra V. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol. 29: 1203-1210.
  • Martínez-Ricarte F, Mayor R, Martínez-Sáez E, Rubio-Pérez C, Pineda E, Cordero E, Cicuéndez M, Poca MA, Lopez-Bigas N, Ramón Y Cajal S, Vieito M, Carles J, Tabernero J, Vivancos A, Gallego S, Graus F, Sahuquillo J, Seoane J. Molecular Diagnosis of Diffuse Gliomas through Sequencing of Cell-Free Circulating Tumor DNA from Cerebrospinal Fluid. Clin Cancer Res. 24: 2812-2819.
  • Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel J M, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer H G, Vivancos A. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017 Oct 1;28(10):2451-2457.
  • García-Foncillas J, Alba E, Aranda E, Díaz-Rubio E, López-López R, Tabernero J, Vivancos A. Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review. Ann Oncol. 2017 Dec 1;28(12):2943-2949.
  • Dienstmann R, Elez E, Argiles G, Matos I, Sanz-Garcia E, Ortiz C, Macarulla T, Capdevila J, Alsina M, Sauri T, Verdaguer H, Vilaro M, Ruiz-Pace F, Viaplana C, Garcia A, Landolfi S, Palmer HG, Nuciforo P, Rodon J, Vivancos A, Tabernero J. Analysis of mutant allele fractions in driver genes in colorectal cancer – biological and clinical insights. Mol Oncol. 2017 Sep;11(9):1263-1272.
  • Grasselli J, Elez E, Caratù G, Matito J, Santos C, Macarulla T, Vidal J, Garcia M, Viéitez JM, Paéz D, Falcó E, Lopez Lopez C, Aranda E, Jones F, Sikri V, Nuciforo P, Fasani R, Tabernero J, Montagut C, Azuara D, Dienstmann R, Salazar R, Vivancos A. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann Oncol. 2017 Jun 1;28(6):1294-1301.
  • Pérez-Alea M, Vivancos A, Caratú G, Matito J, Ferrer B, Hernandez-Losa J, Cortés J, Muñoz E, Garcia-Patos V, Recio JA. Genetic profile of GNAQ-mutated blue melanocytic neoplasms reveals mutations in genes linked to genomic instability and the PI3K pathway. Oncotarget. 2016 May 10;7(19):28086-95. doi: 10.18632/oncotarget.8578.
  • Arqués O, Chicote I, Puig I, Tenbaum SP, Argilés G, Dienstmann R, Fernández N, Caratù G, Matito J, Silberschmidt D, Rodon J, Landolfi S, Prat A, Espín E, Charco R, Nuciforo P, Vivancos A, Shao W, Tabernero J, Palmer HG. Tankyrase Inhibition Blocks Wnt/β-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer. Clin Cancer Res. 2016 Feb 1;22(3):644-56. doi: 10.1158/1078-0432.CCR-14-3081.
  • Ibarrola-Villava M, Fleitas T, Llorca-Cardeñosa MJ, Mongort C, Alonso E, Navarro S, Burgues O, Vivancos A, Cejalvo JM, Perez-Fidalgo JA, Roselló S, Ribas G, Cervantes A. Determination of somatic oncogenic mutations linked to target-based therapies using MassARRAY technology. Oncotarget. 2016 Apr 19;7(16):22543-55. doi: 10.18632/oncotarget.8002.
  • Alves-Rodrigues I, Ferreira PG, Moldón A, Vivancos AP, Hidalgo E, Guigó R, Ayté J. Spatiotemporal Control of Forkhead Binding to DNA Regulates the Meiotic Gene Expression Program. Cell Rep. 2016 Feb 2;14(4):885-95. doi: 10.1016/j.celrep.2015.12.074.
  • Vivancos A, Caratú G, Matito J, Muñoz E, Ferrer B, Hernández-Losa J, Bodet D, Pérez-Alea M, Cortés J, Garcia-Patos V, Recio JA. Genetic evolution of nevus of Ota reveals clonal heterogeneity acquiring BAP1 and TP53 mutations. Pigment Cell Melanoma Res. 2016 Mar;29(2):247-53. doi: 10.1111/pcmr.12452.
  • Yus E, Güell M, Vivancos AP, Chen WH, Lluch-Senar M, Delgado J, Gavin AC, Bork P, Serrano L. Transcription start site associated RNAs in bacteria. Mol. Syst. Biol. 2012; 8: 585
  • Esteve-Codina A, Kofler R, Himmelbauer H, Ferretti L, Vivancos AP, Groenen MA, Folch JM, Rodríguez MC, Pérez-Enciso M. Partial short-read sequencing of a highly inbred Iberian pig and genomics inference thereof. Heredity (Edinb) 2011 Sep; 107(3): 256-64
  • Zuin A, Carmona M, Morales-Ivorra I, Gabrielli N, Vivancos AP, Ayté J, Hidalgo E. Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway. EMBO J. 2010 Mar; 29(5): 981-91
  • Vivancos AP, Castillo EA, Biteau B, Nicot C, Ayté J, Toledano MB, Hidalgo E. A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway. Proc. Natl. Acad. Sci. U.S.A. 2005 Jun; 102(25): 8875-80
  • Vivancos AP, Castillo EA, Jones N, Ayté J, Hidalgo E. Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration. Mol. Microbiol. 2004 Jun; 52(5): 1427-35
  • Castillo EA, Vivancos AP, Jones N, Ayté J, Hidalgo E. Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1. J. Biol. Chem. 2003 Oct; 278(42): 40565-72