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2. Evolution and Clinical Impact of EGFR Mutations in Circulating Free DNA in the BELIEF Trial

Author

Molina-Vila, Miguel-Angel, Stahel, Rolf A., Dafni, Urania, Jordana-Ariza, Núria, Balada-Bel, Ariadna, Garzón-Ibáñez, Mónica, García-Peláez, Beatriz, Mayo-de-las-Casas, Clara, Felip, Enriqueta, Curioni Fontecedro, Alessandra, Gautschi, Oliver, Peters, Solange, Massutí, Bartomeu, Palmero, Ramon, Ponce Aix, Santiago, Carcereny, Enric, Früh, Martin, Pless, Miklos, Popat, Sanjay, Cuffe, Sinead, Bidoli, Paolo, Kammler, Roswitha, Roschitzki-Voser, Heidi, Tsourti, Zoi, Karachaliou, Niki, and Rosell, Rafael

Published
2020
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3. Fluorescence In Situ Hybridization (FISH) for the Characterization and Monitoring of Primary Cultures from Human Tumors

Author

Román-Lladó, Ruth, primary, Aguado, Cristina, additional, Jordana-Ariza, Núria, additional, Roca-Arias, Jaume, additional, Rodríguez, Sonia, additional, Aldeguer, Erika, additional, Garzón-Ibañez, Mónica, additional, García-Peláez, Beatriz, additional, Vives-Usano, Marta, additional, Giménez-Capitán, Ana, additional, Aguilar, Andrés, additional, Martinez-Bueno, Alejandro, additional, Cao, María Gonzalez, additional, García-Casabal, Florencia, additional, Viteri, Santiago, additional, Mayo de las Casas, Clara, additional, Rosell, Rafael, additional, and Molina-Vila, Miguel Angel, additional

Published
2023
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4. Defining Optimal Conditions for Tumor Extracellular Vesicle DNA Extraction for Mutation Profiling

Author

Elzanowska, Julia, primary, Berrocal, Laura, additional, García-Peláez, Beatriz, additional, Vives-Usano, Marta, additional, Sebo, Beatriz Passos, additional, Maia, Joana, additional, Batista, Silvia, additional, Teppo, Jaakko, additional, Varjosalo, Markku, additional, Moraes, Maria Carolina Strano, additional, Molina-Vila, Miguel Ángel, additional, and Costa-Silva, Bruno, additional

Published
2022
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5. Abstract CT107: Correlation of biomarkers and clinical benefit of intratumoral BO112 and pembrolizumab in patients with anti PD1 refractory melanoma

Author

Roman, Ruth, primary, Saiag, Philippe, additional, Dutriaux, Caroline, additional, de la Cruz Merino, Luis, additional, Castanon, Eduardo, additional, Sanmamed, Miguel F., additional, Robert, Caroline, additional, Rodríguez-Moreno, Juan F., additional, Cerezuela-Fuentes, Pablo, additional, Arance, Ana M., additional, Cao, María González, additional, Montaudié, Henry, additional, Criado, María Pilar López, additional, Charles, Julie, additional, Berrocal, Alfonso, additional, del Carmen Álamo de la Gala, María, additional, de Miguel, Enrique, additional, Funk-Brentano, Elisa, additional, Prey, Sorilla, additional, Muñoz-Couselo, Eva, additional, Abreu, Delvys Rodríguez, additional, Martín-Liberal, Juan, additional, Escuin-Ordinas, Helena, additional, Branum, Mark, additional, Macia, Sonia, additional, Quintero, Marisol, additional, López, Javier Sánchez, additional, Chaney, Marya F., additional, García-Peláez, Beatriz, additional, Vives-Usano, Marta, additional, Molina, Miguel Ángel, additional, Dalle, Stéphane, additional, and Márquez-Rodas, Iván, additional

Published
2022
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6. Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial

Author

Romero, Atocha, Jantus-Lewintre, Eloisa, García-Peláez, Beatriz, Royuela, Ana., Insa, Amelia, Bernabé-Caro, Reyes, Provencio, Mariano, and Universidad de Sevilla. Departamento de Medicina

Abstract

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80–0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86–0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs.

Published
2021

7. Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial

Author

Universidad de Sevilla. Departamento de Medicina, Romero, Atocha, Jantus-Lewintre, Eloisa, García-Peláez, Beatriz, Royuela, Ana., Insa, Amelia, Bernabé-Caro, Reyes, Provencio, Mariano, Universidad de Sevilla. Departamento de Medicina, Romero, Atocha, Jantus-Lewintre, Eloisa, García-Peláez, Beatriz, Royuela, Ana., Insa, Amelia, Bernabé-Caro, Reyes, and Provencio, Mariano

Abstract

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80–0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86–0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs.

Published
2021

8. Comprehensive cross‐platform comparison of methods for non‐invasive EGFR mutation testing: results of the RING observational trial

Author

Romero, Atocha, primary, Jantus‐Lewintre, Eloisa, additional, García‐Peláez, Beatriz, additional, Royuela, Ana, additional, Insa, Amelia, additional, Cruz, Patricia, additional, Collazo, Ana, additional, Pérez Altozano, Javier, additional, Vidal, Oscar Juan, additional, Diz, Pilar, additional, Cobo, Manuel, additional, Hernández, Berta, additional, Vázquez Estevez, Sergio, additional, Benítez, Gretel, additional, Guirado, Maria, additional, Majem, Margarita, additional, Bernabé, Reyes, additional, Ortega, Ana Laura, additional, Blasco, Ana, additional, Bosch‐Barrera, Joaquim, additional, Jurado, Jose M., additional, García González, Jorge, additional, Viteri, Santiago, additional, Garcia Giron, Carlos, additional, Massutí, Bartomeu, additional, Lopez Martín, Ana, additional, Rodriguez‐Festa, Alejandro, additional, Calabuig‐Fariñas, Silvia, additional, Molina‐Vila, Miguel Ángel, additional, and Provencio, Mariano, additional

Published
2020
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9. Abstract 3175: Copy number gains of clinically relevant genes in advanced non small cell lung cancer patients

Author

Ariza, Núria Jordana-, primary, Garzón, Mónica, additional, García-Peláez, Beatriz, additional, Román, Ruth, additional, Alamillo, Jordi Bertrán-, additional, Rodriguez, Sonia, additional, Aldeguer, Erika, additional, García-Román, Silvia, additional, Viteri, Santiago, additional, Aguilar, Andrés, additional, Cao, María González, additional, Bueno, Alejandro Martínez-, additional, Vila, Miguel Angel Molina, additional, Costa, Rafael Rosell, additional, and de las Casas, Clara Mayo, additional

Published
2020
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10. Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Author

Villatoro, Sergio, primary, Mayo‐de‐las‐Casas, Clara, additional, Jordana‐Ariza, Núria, additional, Viteri‐Ramírez, Santiago, additional, Garzón‐Ibañez, Mónica, additional, Moya‐Horno, Irene, additional, García‐Peláez, Beatriz, additional, González‐Cao, María, additional, Malapelle, Umberto, additional, Balada‐Bel, Ariadna, additional, Martínez‐Bueno, Alejandro, additional, Campos, Raquel, additional, Reguart, Noemí, additional, Majem, Margarita, additional, Blanco, Remei, additional, Blasco, Ana, additional, Catalán, María J., additional, González, Xavier, additional, Troncone, Giancarlo, additional, Karachaliou, Niki, additional, Rosell, Rafael, additional, and Molina‐Vila, Miguel A., additional

Published
2019
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11. Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning

Author

Vilà Ruth, García-Peláez Beatriz, and Remesar Xavier

Subjects
Gynecology and obstetrics, RG1-991, Reproduction, QH471-489
Abstract

Abstract Background In rats, oral oleoyl-estrone (OE) decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. Methods Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day). Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. Results Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. Conclusion The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood.

Published
2008
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12. Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform

Author

Mayo de las Casas, Clara, primary, Garzón-Ibañez, Mónica, additional, Jordana-Ariza, Núria, additional, Viteri-Ramírez, Santiago, additional, Moya-Horno, Irene, additional, Karachaliou, Niki, additional, Yeste, Zaira, additional, Campos, Raquel, additional, Villatoro, Sergi, additional, Balada-Bel, Ariadna, additional, García-Peláez, Beatriz, additional, Reguart, Noemí, additional, Teixidó, Cristina, additional, Jantús, Eloisa, additional, Calabuig, Silvia, additional, Aguado, Cristina, additional, Giménez-Capitán, Ana, additional, Román-Lladó, Ruth, additional, Pérez-Rosado, Ana, additional, Catalán, Maria José, additional, Bertrán-Alamillo, Jordi, additional, García-Román, Silvia, additional, Rodriguez, Sonia, additional, Alonso, Lidia, additional, Aldeguer, Erika, additional, Martínez-Bueno, Alejandro, additional, González-Cao, Maria, additional, Aguilar Hernandez, Andrés, additional, Garcia-Mosquera, Juan, additional, de los Llanos Gil, Maria, additional, Fernandez, Manuel, additional, Rosell, Rafael, additional, and Molina-Vila, Miguel Ángel, additional

Published
2018
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13. An update on liquid biopsy analysis for diagnostic and monitoring applications in non-small cell lung cancer

Author

Mayo-de-las-Casas, Clara, primary, Garzón Ibáñez, Mónica, additional, Jordana-Ariza, Núria, additional, García-Peláez, Beatriz, additional, Balada-Bel, Ariadna, additional, Villatoro, Sergio, additional, Malapelle, Umberto, additional, Karachaliou, Niki, additional, Troncone, Giancarlo, additional, Rosell, Rafael, additional, and Molina-Vila, Miguel Angel, additional

Published
2017
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14. Evolution and Clinical Impact of EGFRMutations in Circulating Free DNA in the BELIEF Trial

Author

Molina-Vila, Miguel-Angel, Stahel, Rolf A., Dafni, Urania, Jordana-Ariza, Núria, Balada-Bel, Ariadna, Garzón-Ibáñez, Mónica, García-Peláez, Beatriz, Mayo-de-las-Casas, Clara, Felip, Enriqueta, Curioni Fontecedro, Alessandra, Gautschi, Oliver, Peters, Solange, Massutí, Bartomeu, Palmero, Ramon, Ponce Aix, Santiago, Carcereny, Enric, Früh, Martin, Pless, Miklos, Popat, Sanjay, Cuffe, Sinead, Bidoli, Paolo, Kammler, Roswitha, Roschitzki-Voser, Heidi, Tsourti, Zoi, Karachaliou, Niki, and Rosell, Rafael

Abstract

Longitudinal evaluation of mutations in blood samples was a prespecified secondary objective in the BELIEF trial of erlotinib and bevacizumab in advanced EGFR-positive NSCLC. Here, we report the testing results and explore the correlation of EGFRstatus in blood with clinical outcomes.

Published
2020
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15. Liquid Biopsy in Non-Small Cell Lung Cancer

Author

Molina-Vila, Miguel A., primary, Mayo-de-las-Casas, Clara, additional, Giménez-Capitán, Ana, additional, Jordana-Ariza, Núria, additional, Garzón, Mónica, additional, Balada, Ariadna, additional, Villatoro, Sergi, additional, Teixidó, Cristina, additional, García-Peláez, Beatriz, additional, Aguado, Cristina, additional, Catalán, María José, additional, Campos, Raquel, additional, Pérez-Rosado, Ana, additional, Bertran-Alamillo, Jordi, additional, Martínez-Bueno, Alejandro, additional, Gil, María-de-los-Llanos, additional, González-Cao, María, additional, González, Xavier, additional, Morales-Espinosa, Daniela, additional, Viteri, Santiago, additional, Karachaliou, Niki, additional, and Rosell, Rafael, additional

Published
2016
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16. An update on liquid biopsy analysis for diagnostic and monitoring applications in non-small cell lung cancer.

Author

Mayo-de-las-Casas, Clara, Garzón Ibáñez, Mónica, Jordana-Ariza, Núria, García-Peláez, Beatriz, Balada-Bel, Ariadna, Villatoro, Sergio, Malapelle, Umberto, Karachaliou, Niki, Troncone, Giancarlo, Rosell, Rafael, and Molina-Vila, Miguel Angel

Abstract

Introduction: Collection of tumor samples is not always feasible in non-small cell lung cancer (NSCLC) patients, and circulating free DNA (cfDNA) extracted from blood represents a viable alternative. Different sensitive platforms have been developed for genetic cfDNA testing, some of which are already in clinical use. However, several difficulties remain, particularly the lack of standardization of these methodologies. Areas covered: Here, the authors present a review of the literature to update the applicability of cfDNA for diagnosis and monitoring of NSCLC patients. Expert commentary: Detection of somatic alterations in cfDNA is already in use in clinical practice and provides valuable information for patient management. Monitoring baseline alterations and emergence of resistance mutations is one of the most important clinical applications and can be used to non-invasively track disease evolution. Today, different technologies are available for cfDNA analysis, including whole-genome or exome sequencing and targeted methods that focus on a selection of genes of interest in a specific disease. In the case of Next Generation Sequencing (NGS) approaches, in depth coverage of candidate mutation loci can be achieved by selecting a limited number of targeted genes. [ABSTRACT FROM PUBLISHER]

Published
2018
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17. Measurement of total estrone content in foods. Application to dairy products

Author

García Peláez, Beatriz, Ferrer Lorente, Raquel, Gómez-Ollés, S., Fernández López, José Antonio, Remesar Betlloch, Xavier, Alemany, Marià, 1946, and Universitat de Barcelona

Subjects
Food, Aliments, Productes lactis, Dairy products
Abstract

Estrone is a powerful growth-inducing hormone that is present in milk, mainly in the form of fatty acid esters, at concentrations that promote growth in experimental animals. We present here a method useful for the measurement of this natural hormone in foods and applied it to several common dairy products. Samples were frozen, finely powdered, and lyophilized then extracted with trichloromethane/methanol; the dry extract was saponified with potassium hydroxide. The free estrone evolved was extracted with ethyl acetate and was used for the estimation of total estrone content through radioimmunoassay. Application of the method to dairy products showed high relative levels of total estrone (essentially acyl-estrone) in milk, in the range of 1 ¿M, which were halved in skimmed milk. Free estrone levels were much lower, in the nanomolar range. A large proportion of estrone esters was present in all other dairy products, fairly correlated with their fat content. The amount of estrone carried by milk is well within the range, where its intake may exert a physiological response in the sucklings for which it is provided. These growth-inducing and energy expenditure-lowering effects may affect humans ingesting significant amounts of dairy products.

Published
2004

20. Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.

Author

Romero A, Jantus-Lewintre E, García-Peláez B, Royuela A, Insa A, Cruz P, Collazo A, Pérez Altozano J, Vidal OJ, Diz P, Cobo M, Hernández B, Vázquez Estevez S, Benítez G, Guirado M, Majem M, Bernabé R, Ortega AL, Blasco A, Bosch-Barrera J, Jurado JM, García González J, Viteri S, Garcia Giron C, Massutí B, Lopez Martín A, Rodriguez-Festa A, Calabuig-Fariñas S, Molina-Vila MÁ, and Provencio M

Subjects
Adult, Aged, Aged, 80 and over, Biopsy, Cohort Studies, DNA, Neoplasm genetics, DNA, Neoplasm isolation & purification, ErbB Receptors genetics, Exons genetics, Female, Gene Frequency genetics, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Predictive Value of Tests, Sensitivity and Specificity, Sequence Deletion genetics, DNA Mutational Analysis methods, Mutation genetics
Abstract

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Published
2021
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21. Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform.

Author

Mayo de Las Casas C, Garzón-Ibañez M, Jordana-Ariza N, Viteri-Ramírez S, Moya-Horno I, Karachaliou N, Yeste Z, Campos R, Villatoro S, Balada-Bel A, García-Peláez B, Reguart N, Teixidó C, Jantús E, Calabuig S, Aguado C, Giménez-Capitán A, Román-Lladó R, Pérez-Rosado A, Catalán MJ, Bertrán-Alamillo J, García-Román S, Rodriguez S, Alonso L, Aldeguer E, Martínez-Bueno A, González-Cao M, Aguilar Hernandez A, Garcia-Mosquera J, de Los Llanos Gil M, Fernandez M, Rosell R, and Molina-Vila MÁ

Abstract

Background: In a significant percentage of advanced non-small cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses at time to progression. We prospectively analyzed the appearance of genetic alterations associated with resistance in liquid biopsies of advanced NSCLC patients progressing to targeted therapies using the NGS platform., Methods: A total of 24 NSCLC patients were included in the study, 22 progressing to tyrosine kinase inhibitors and two to other treatments. Liquid biopsies samples were obtained and analyzed using the GeneRead TM QIAact Lung DNA UMI Panel, designed to enrich specific target regions and containing 550 variant positions in 19 selected genes frequently altered in lung cancer tumors. Previously, a retrospective validation of the panel was performed in clinical samples., Results: Of the 21 patients progressing to tyrosine kinase inhibitors with valid results in liquid biopsy, NGS analysis identified a potential mechanism of resistance in 12 (57%). The most common were acquired mutations in ALK and EGFR , which appeared in 8/21 patients (38%), followed by amplifications in 5/21 patients (24%), and KRAS mutations in one patient (5%). Loss of the p.T790M was also identified in two patients progressing to osimertinib. Three of the 21 (14%) patients presented two or more concomitant alterations associated with resistance. Finally, an EGFR amplification was found in the only patient progressing to immunotherapy included in the study., Conclusions: NGS analysis in liquid biopsies of patients progressing to targeted therapies using the GeneReader platform is feasible and can help the oncologist to make treatment decisions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2018.10.12). The series “Targeted Therapy and Non-Small Cell Lung Cancer: A New Era?” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Published
2019
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