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146 results on '"Tornero, E."'

4. P1.01-01 Frequency of Germline Mutations in Patients with Non-small Cell Lung Cancer (NSCLC) Harboring Actionable DRIVER Alterations (G-DRIVER)

Author

Jové, M., primary, Gausachs, M., additional, Bosch-Barrera, J., additional, Carcereny, E., additional, Teule, A., additional, Mosteiro, M., additional, Pineda, M., additional, Tornero, E., additional, Palmero, R., additional, Vilarino, N., additional, Ruffinelli, J.C., additional, Mesia, C., additional, Saldaña, J., additional, Cuellar, A., additional, Brenes, J., additional, Hernandez, A., additional, Fina, C., additional, Brunet, J., additional, Domenech, M., additional, Moran, T., additional, Sais, E., additional, Lazaro, C., additional, and Nadal, E., additional

Published
2023
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9. Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study

Author

Barcenilla, F., Pérez-Villar, F., Prats-Gispert, L., Cisterna, R., Ibarra, S., López, Í., Santamaría, J.M., Cabo, J., García, D., Lora-Tamayo, J., Murillo, O., Pedrero, S., Álvarez-Parrondo, S., Muedra-Font, R., Raya-Fernández, C., Rodríguez-Alonso, C., Moreno, A., Blanco-Martínez-de-Morentin, M.A., Cabo-Magadan, R., Combalia, A., García, S., Martínez-Pastor, J.C., Tornero, E., Merino-Pérez, J., Montejo, J.M., Alier, A., Horcajada, J.P., Plasencia, V., Puig, L., Auñon, Á., Blanco, A., García-Cañete, J., Sandoval, E., Fakkas-Fernández, M., Garcés-Zarzalejo, C., Fariñas-Alvarez, C., Fariñas, M.C., Martinez-Martinez, L., Salas-Venero, C., Cobo, J., Ruiz-Carbajosa, P., Jordán, M., Crusi, X., Marinescu, C., Montaner, F., Ramírez, A., Corona, P.S., Lung, M., Muniain-Ezcurra, M.Á., Peñas-Espinar, C., Suárez, A.I., Álvarez, R., Cordero, J.-A., López-Pliego, M., Palomino, J., Puente, A., Benito, N., Franco, M., Ribera, A., Soriano, A., Rodriguez-Pardo, D., Sorlí, L., Fresco, G., Fernández-Sampedro, M., Dolores del Toro, M., Guío, L., Sánchez-Rivas, E., Bahamonde, A., Riera, M., Esteban, J., Baraia-Etxaburu, J.M., Martínez-Alvarez, J., Jover-Sáenz, A., Dueñas, C., Ramos, A., Sobrino, B., Euba, G., Morata, L., Pigrau, C., Coll, P., Mur, I., and Ariza, J.

Published
2016
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14. Comprehensive analysis and ACMG-based classification ofCHEK2variants in hereditary cancer patients

Author

Vargas-Parra, G, del Valle, J, Rofes, P, Gausachs, M, Stradella, A, Moreno-Cabrera, JM, Velasco, A, Tornero, E, Menendez, M, Munoz, X, Iglesias, S, Lopez-Doriga, A, Azuara, D, Campos, O, Cuesta, R, Darder, E, de Cid, R, Gonzalez, S, Teule, A, Navarro, M, Brunet, J, Capella, G, Pineda, M, Feliubadalo, L, and Lazaro, C

Subjects
hereditary cancer, low penetrance, molecular diagnosis, variant classification, CHEK2, risk allele
Abstract

CHEK2variants are associated with intermediate breast cancer risk, among other cancers. We aimed to comprehensively describeCHEK2variants in a Spanish hereditary cancer (HC) cohort and adjust the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. First, threeCHEK2frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients. After, the wholeCHEK2coding region was analyzed by next-generation sequencing in 1848 prospective patients with HC suspicion. We refined ACMG-AMP criteria and applied different combined rules to classifyCHEK2variants and define risk alleles. We identified 10CHEK2null variants, 6 missense variants with discordant interpretation in ClinVar database, and 35 additional variants of unknown significance. Twelve variants were classified as (likely)-pathogenic; two can also be considered "established risk-alleles" and one as "likely risk-allele." The prevalence of (likely)-pathogenic variants in the HC cohort was 0.8% (1.3% in breast cancer patients and 1.0% in hereditary nonpolyposis colorectal cancer patients). Here, we provide ACMG adjustment guidelines to classifyCHEK2variants. We hope that this study would be useful for variant classification of other genes with low effect variants.

Published
2020

16. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.

Author

Feroce I., Schoenwiese U., Seggewiss J., Solanes A., Steinemann D., Stiller M., Stoppa-Lyonnet D., Sullivan K.J., Susman R., Sutter C., Tavtigian S.V., Teo S.H., Teule A., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tornero E., Torngren T., Torres-Esquius S., Toss A., Trainer A.H., Tucker K.M., van Asperen C.J., van Mackelenbergh M.T., Varesco L., Vargas-Parra G., Varon R., Vega A., Velasco A., Vesper A.-S., Viel A., Vreeswijk M.P.G., Wagner S.A., Waha A., Walker L.C., Walters R.J., Wang-Gohrke S., Weber B.H.F., Weichert W., Wieland K., Wiesmuller L., Witzel I., Wockel A., Woodward E.R., Zachariae S., Zampiga V., Zeder-Goss C., Investigators K., Lazaro C., De Nicolo A., Radice P., Engel C., Schmutzler R.K., Goldgar D.E., Spurdle A.B., Harris M., Parsons M.T., Tudini E., Li H., Hahnen E., Wappenschmidt B., Feliubadalo L., Aalfs C.M., Agata S., Aittomaki K., Alducci E., Alonso-Cerezo M.C., Arnold N., Auber B., Austin R., Azzollini J., Balmana J., Barbieri E., Bartram C.R., Blanco A., Blumcke B., Bonache S., Bonanni B., Borg A., Bortesi B., Brunet J., Bruzzone C., Bucksch K., Cagnoli G., Caldes T., Caliebe A., Caligo M.A., Calvello M., Capone G.L., Caputo S.M., Carnevali I., Carrasco E., Caux-Moncoutier V., Cavalli P., Cini G., Clarke E.M., Concolino P., Cops E.J., Cortesi L., Couch F.J., Darder E., de la Hoya M., Dean M., Debatin I., Del Valle J., Delnatte C., Derive N., Diez O., Ditsch N., Domchek S.M., Dutrannoy V., Eccles D.M., Ehrencrona H., Enders U., Evans D.G., Farra C., Faust U., Felbor U., Fine M., Foulkes W.D., Galvao H.C.R., Gambino G., Gehrig A., Gensini F., Gerdes A.-M., Germani A., Giesecke J., Gismondi V., Gomez C., Gomez Garcia E.B., Gonzalez S., Grau E., Grill S., Gross E., Guerrieri-Gonzaga A., Guillaud-Bataille M., Gutierrez-Enriquez S., Haaf T., Hackmann K., Hansen T.V.O., Hauke J., Heinrich T., Hellebrand H., Herold K.N., Honisch E., Horvath J., Houdayer C., Hubbel V., Iglesias S., Izquierdo A., James P.A., Janssen L.A.M., Jeschke U., Kaulfuss S., Keupp K., Kiechle M., Kolbl A., Krieger S., Kruse T.A., Kvist A., Lalloo F., Larsen M., Lattimore V.L., Lautrup C., Ledig S., Leinert E., Lewis A.L., Lim J., Loeffler M., Lopez-Fernandez A., Lucci-Cordisco E., Maass N., Manoukian S., Marabelli M., Matricardi L., Meindl A., Michelli R.D., Moghadasi S., Moles-Fernandez A., Montagna M., Montalban G., Monteiro A.N., Montes E., Mori L., Moserle L., Muller C.R., Mundhenke C., Naldi N., Nathanson K.L., Navarro M., Nevanlinna H., Nichols C.B., Niederacher D., Nielsen H.R., Ong K.-R., Pachter N., Palmero E.I., Papi L., Pedersen I.S., Peissel B., Perez-Segura P., Pfeifer K., Pineda M., Pohl-Rescigno E., Poplawski N.K., Porfirio B., Quante A.S., Ramser J., Reis R.M., Revillion F., Rhiem K., Riboli B., Ritter J., Rivera D., Rofes P., Rump A., Salinas M., Sanchez de Abajo A.M., Schmidt G., Feroce I., Schoenwiese U., Seggewiss J., Solanes A., Steinemann D., Stiller M., Stoppa-Lyonnet D., Sullivan K.J., Susman R., Sutter C., Tavtigian S.V., Teo S.H., Teule A., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tornero E., Torngren T., Torres-Esquius S., Toss A., Trainer A.H., Tucker K.M., van Asperen C.J., van Mackelenbergh M.T., Varesco L., Vargas-Parra G., Varon R., Vega A., Velasco A., Vesper A.-S., Viel A., Vreeswijk M.P.G., Wagner S.A., Waha A., Walker L.C., Walters R.J., Wang-Gohrke S., Weber B.H.F., Weichert W., Wieland K., Wiesmuller L., Witzel I., Wockel A., Woodward E.R., Zachariae S., Zampiga V., Zeder-Goss C., Investigators K., Lazaro C., De Nicolo A., Radice P., Engel C., Schmutzler R.K., Goldgar D.E., Spurdle A.B., Harris M., Parsons M.T., Tudini E., Li H., Hahnen E., Wappenschmidt B., Feliubadalo L., Aalfs C.M., Agata S., Aittomaki K., Alducci E., Alonso-Cerezo M.C., Arnold N., Auber B., Austin R., Azzollini J., Balmana J., Barbieri E., Bartram C.R., Blanco A., Blumcke B., Bonache S., Bonanni B., Borg A., Bortesi B., Brunet J., Bruzzone C., Bucksch K., Cagnoli G., Caldes T., Caliebe A., Caligo M.A., Calvello M., Capone G.L., Caputo S.M., Carnevali I., Carrasco E., Caux-Moncoutier V., Cavalli P., Cini G., Clarke E.M., Concolino P., Cops E.J., Cortesi L., Couch F.J., Darder E., de la Hoya M., Dean M., Debatin I., Del Valle J., Delnatte C., Derive N., Diez O., Ditsch N., Domchek S.M., Dutrannoy V., Eccles D.M., Ehrencrona H., Enders U., Evans D.G., Farra C., Faust U., Felbor U., Fine M., Foulkes W.D., Galvao H.C.R., Gambino G., Gehrig A., Gensini F., Gerdes A.-M., Germani A., Giesecke J., Gismondi V., Gomez C., Gomez Garcia E.B., Gonzalez S., Grau E., Grill S., Gross E., Guerrieri-Gonzaga A., Guillaud-Bataille M., Gutierrez-Enriquez S., Haaf T., Hackmann K., Hansen T.V.O., Hauke J., Heinrich T., Hellebrand H., Herold K.N., Honisch E., Horvath J., Houdayer C., Hubbel V., Iglesias S., Izquierdo A., James P.A., Janssen L.A.M., Jeschke U., Kaulfuss S., Keupp K., Kiechle M., Kolbl A., Krieger S., Kruse T.A., Kvist A., Lalloo F., Larsen M., Lattimore V.L., Lautrup C., Ledig S., Leinert E., Lewis A.L., Lim J., Loeffler M., Lopez-Fernandez A., Lucci-Cordisco E., Maass N., Manoukian S., Marabelli M., Matricardi L., Meindl A., Michelli R.D., Moghadasi S., Moles-Fernandez A., Montagna M., Montalban G., Monteiro A.N., Montes E., Mori L., Moserle L., Muller C.R., Mundhenke C., Naldi N., Nathanson K.L., Navarro M., Nevanlinna H., Nichols C.B., Niederacher D., Nielsen H.R., Ong K.-R., Pachter N., Palmero E.I., Papi L., Pedersen I.S., Peissel B., Perez-Segura P., Pfeifer K., Pineda M., Pohl-Rescigno E., Poplawski N.K., Porfirio B., Quante A.S., Ramser J., Reis R.M., Revillion F., Rhiem K., Riboli B., Ritter J., Rivera D., Rofes P., Rump A., Salinas M., Sanchez de Abajo A.M., and Schmidt G.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.Copyright © 2019 Wiley Periodicals, Inc.

Published
2019

17. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, MT, Tudini, E, Li, H, Hahnen, E, Wappenschmidt, B, Feliubadalo, L, Aalfs, CM, Agata, S, Aittomaki, K, Alducci, E, Concepcion Alonso-Cerezo, M, Arnold, N, Auber, B, Austin, R, Azzollini, J, Balmana, J, Barbieri, E, Bartram, CR, Blanco, A, Bluemcke, B, Bonache, S, Bonanni, B, Borg, A, Bortesi, B, Brunet, J, Bruzzone, C, Bucksch, K, Cagnoli, G, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Capone, GL, Caputo, SM, Carnevali, I, Carrasco, E, Caux-Moncoutier, V, Cavalli, P, Cini, G, Clarke, EM, Concolino, P, Cops, EJ, Cortesi, L, Couch, FJ, Darder, E, de la Hoya, M, Dean, M, Debatin, I, Del Valle, J, Delnatte, C, Derive, N, Diez, O, Ditsch, N, Domchek, SM, Dutrannoy, V, Eccles, DM, Ehrencrona, H, Enders, U, Evans, DG, Farra, C, Faust, U, Felbor, U, Feroce, I, Fine, M, Foulkes, WD, Galvao, HC, Gambino, G, Gehrig, A, Gensini, F, Gerdes, A-M, Germani, A, Giesecke, J, Gismondi, V, Gomez, C, Garcia, EBG, Gonzalez, S, Grau, E, Grill, S, Gross, E, Guerrieri-Gonzaga, A, Guillaud-Bataille, M, Gutierrez-Enriquez, S, Haaf, T, Hackmann, K, Hansen, TV, Harris, M, Hauke, J, Heinrich, T, Hellebrand, H, Herold, KN, Honisch, E, Horvath, J, Houdayer, C, Huebbel, V, Iglesias, S, Izquierdo, A, James, PA, Janssen, LA, Jeschke, U, Kaulfuss, S, Keupp, K, Kiechle, M, Koelbl, A, Krieger, S, Kruse, TA, Kvist, A, Lalloo, F, Larsen, M, Lattimore, VL, Lautrup, C, Ledig, S, Leinert, E, Lewis, AL, Lim, J, Loeffler, M, Lopez-Fernandez, A, Lucci-Cordisco, E, Maass, N, Manoukian, S, Marabelli, M, Matricardi, L, Meindl, A, Michelli, RD, Moghadasi, S, Moles-Fernandez, A, Montagna, M, Montalban, G, Monteiro, AN, Montes, E, Mori, L, Moserle, L, Mueller, CR, Mundhenke, C, Naldi, N, Nathanson, KL, Navarro, M, Nevanlinna, H, Nichols, CB, Niederacher, D, Nielsen, HR, Ong, K-R, Pachter, N, Palmero, E, Papi, L, Pedersen, IS, Peissel, B, Perez-Segura, P, Pfeifer, K, Pineda, M, Pohl-Rescigno, E, Poplawski, NK, Porfirio, B, Quante, AS, Ramser, J, Reis, RM, Revillion, F, Rhiem, K, Riboli, B, Ritter, J, Rivera, D, Rofes, P, Rump, A, Salinas, M, Sanchez de Abajo, AM, Schmidt, G, Schoenwiese, U, Seggewiss, J, Solanes, A, Steinemann, D, Stiller, M, Stoppa-Lyonnet, D, Sullivan, KJ, Susman, R, Sutter, C, Tavtigian, S, Teo, SH, Teule, A, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tornero, E, Torngren, T, Torres-Esquius, S, Toss, A, Trainer, AH, Tucker, KM, van Asperen, CJ, van Mackelenbergh, MT, Varesco, L, Vargas-Parra, G, Varon, R, Vega, A, Velasco, A, Vesper, A-S, Viel, A, Vreeswijk, MPG, Wagner, SA, Waha, A, Walker, LC, Walters, RJ, Wang-Gohrke, S, Weber, BHF, Weichert, W, Wieland, K, Wiesmueller, L, Witzel, I, Woeckel, A, Woodward, ER, Zachariae, S, Zampiga, V, Zeder-Goss, C, Lazaro, C, De Nicolo, A, Radice, P, Engel, C, Schmutzler, RK, Goldgar, DE, Spurdle, AB, Parsons, MT, Tudini, E, Li, H, Hahnen, E, Wappenschmidt, B, Feliubadalo, L, Aalfs, CM, Agata, S, Aittomaki, K, Alducci, E, Concepcion Alonso-Cerezo, M, Arnold, N, Auber, B, Austin, R, Azzollini, J, Balmana, J, Barbieri, E, Bartram, CR, Blanco, A, Bluemcke, B, Bonache, S, Bonanni, B, Borg, A, Bortesi, B, Brunet, J, Bruzzone, C, Bucksch, K, Cagnoli, G, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Capone, GL, Caputo, SM, Carnevali, I, Carrasco, E, Caux-Moncoutier, V, Cavalli, P, Cini, G, Clarke, EM, Concolino, P, Cops, EJ, Cortesi, L, Couch, FJ, Darder, E, de la Hoya, M, Dean, M, Debatin, I, Del Valle, J, Delnatte, C, Derive, N, Diez, O, Ditsch, N, Domchek, SM, Dutrannoy, V, Eccles, DM, Ehrencrona, H, Enders, U, Evans, DG, Farra, C, Faust, U, Felbor, U, Feroce, I, Fine, M, Foulkes, WD, Galvao, HC, Gambino, G, Gehrig, A, Gensini, F, Gerdes, A-M, Germani, A, Giesecke, J, Gismondi, V, Gomez, C, Garcia, EBG, Gonzalez, S, Grau, E, Grill, S, Gross, E, Guerrieri-Gonzaga, A, Guillaud-Bataille, M, Gutierrez-Enriquez, S, Haaf, T, Hackmann, K, Hansen, TV, Harris, M, Hauke, J, Heinrich, T, Hellebrand, H, Herold, KN, Honisch, E, Horvath, J, Houdayer, C, Huebbel, V, Iglesias, S, Izquierdo, A, James, PA, Janssen, LA, Jeschke, U, Kaulfuss, S, Keupp, K, Kiechle, M, Koelbl, A, Krieger, S, Kruse, TA, Kvist, A, Lalloo, F, Larsen, M, Lattimore, VL, Lautrup, C, Ledig, S, Leinert, E, Lewis, AL, Lim, J, Loeffler, M, Lopez-Fernandez, A, Lucci-Cordisco, E, Maass, N, Manoukian, S, Marabelli, M, Matricardi, L, Meindl, A, Michelli, RD, Moghadasi, S, Moles-Fernandez, A, Montagna, M, Montalban, G, Monteiro, AN, Montes, E, Mori, L, Moserle, L, Mueller, CR, Mundhenke, C, Naldi, N, Nathanson, KL, Navarro, M, Nevanlinna, H, Nichols, CB, Niederacher, D, Nielsen, HR, Ong, K-R, Pachter, N, Palmero, E, Papi, L, Pedersen, IS, Peissel, B, Perez-Segura, P, Pfeifer, K, Pineda, M, Pohl-Rescigno, E, Poplawski, NK, Porfirio, B, Quante, AS, Ramser, J, Reis, RM, Revillion, F, Rhiem, K, Riboli, B, Ritter, J, Rivera, D, Rofes, P, Rump, A, Salinas, M, Sanchez de Abajo, AM, Schmidt, G, Schoenwiese, U, Seggewiss, J, Solanes, A, Steinemann, D, Stiller, M, Stoppa-Lyonnet, D, Sullivan, KJ, Susman, R, Sutter, C, Tavtigian, S, Teo, SH, Teule, A, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tornero, E, Torngren, T, Torres-Esquius, S, Toss, A, Trainer, AH, Tucker, KM, van Asperen, CJ, van Mackelenbergh, MT, Varesco, L, Vargas-Parra, G, Varon, R, Vega, A, Velasco, A, Vesper, A-S, Viel, A, Vreeswijk, MPG, Wagner, SA, Waha, A, Walker, LC, Walters, RJ, Wang-Gohrke, S, Weber, BHF, Weichert, W, Wieland, K, Wiesmueller, L, Witzel, I, Woeckel, A, Woodward, ER, Zachariae, S, Zampiga, V, Zeder-Goss, C, Lazaro, C, De Nicolo, A, Radice, P, Engel, C, Schmutzler, RK, Goldgar, DE, and Spurdle, AB

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

18. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadalo, L., Aalfs, C. M., Agata, S., Aittomaki, K., Alducci, E., Alonso-Cerezo, M. C., Arnold, N., Auber, B., Austin, R., Azzollini, J., Balmana, J., Barbieri, E., Bartram, C. R., Blanco, A., Blumcke, B., Bonache, S., Bonanni, B., Borg, A., Bortesi, B., Brunet, J., Bruzzone, C., Bucksch, K., Cagnoli, G., Caldes, T., Caliebe, A., Caligo, M. A., Calvello, M., Capone, G. L., Caputo, S. M., Carnevali, I., Carrasco, E., Caux-Moncoutier, V., Cavalli, P., Cini, G., Clarke, E. M., Concolino, Paola, Cops, E. J., Cortesi, L., Couch, F. J., Darder, E., de la Hoya, M., Dean, M., Debatin, I., Del Valle, J., Delnatte, C., Derive, N., Diez, O., Ditsch, N., Domchek, S. M., Dutrannoy, V., Eccles, D. M., Ehrencrona, H., Enders, U., Evans, D. G., Farra, C., Faust, U., Felbor, U., Feroce, I., Fine, M., Foulkes, W. D., Galvao, H. C. R., Gambino, G., Gehrig, A., Gensini, F., Gerdes, A. -M., Germani, A., Giesecke, J., Gismondi, V., Gomez, C., Gomez Garcia, E. B., Gonzalez, S., Grau, E., Grill, S., Gross, E., Guerrieri-Gonzaga, A., Guillaud-Bataille, M., Gutierrez-Enriquez, S., Haaf, T., Hackmann, K., Hansen, T. V. O., Harris, M., Hauke, J., Heinrich, T., Hellebrand, H., Herold, K. N., Honisch, E., Horvath, J., Houdayer, C., Hubbel, V., Iglesias, S., Izquierdo, A., James, P. A., Janssen, L. A. M., Jeschke, U., Kaulfuss, S., Keupp, K., Kiechle, M., Kolbl, A., Krieger, S., Kruse, T. A., Kvist, A., Lalloo, F., Larsen, M., Lattimore, V. L., Lautrup, C., Ledig, S., Leinert, E., Lewis, A. L., Lim, J., Loeffler, M., Lopez-Fernandez, A., Lucci Cordisco, Emanuela, Maass, N., Manoukian, S., Marabelli, M., Matricardi, L., Meindl, A., Michelli, R. D., Moghadasi, S., Moles-Fernandez, A., Montagna, M., Montalban, G., Monteiro, A. N., Montes, E., Mori, L., Moserle, L., Muller, C. R., Mundhenke, C., Naldi, N., Nathanson, K. L., Navarro, M., Nevanlinna, H., Nichols, C. B., Niederacher, D., Nielsen, H. R., Ong, K. -R., Pachter, N., Palmero, E. I., Papi, L., Pedersen, I. S., Peissel, B., Perez-Segura, P., Pfeifer, K., Pineda, M., Pohl-Rescigno, E., Poplawski, N. K., Porfirio, B., Quante, A. S., Ramser, J., Reis, R. M., Revillion, F., Rhiem, K., Riboli, B., Ritter, J., Rivera, D., Rofes, P., Rump, A., Salinas, M., Sanchez de Abajo, A. M., Schmidt, G., Schoenwiese, U., Seggewiss, J., Solanes, A., Steinemann, D., Stiller, M., Stoppa-Lyonnet, D., Sullivan, K. J., Susman, R., Sutter, C., Tavtigian, S. V., Teo, S. H., Teule, A., Thomassen, M., Tibiletti, M. G., Tischkowitz, M., Tognazzo, S., Toland, A. E., Tornero, E., Torngren, T., Torres-Esquius, S., Toss, A., Trainer, A. H., Tucker, K. M., van Asperen, C. J., van Mackelenbergh, M. T., Varesco, L., Vargas-Parra, G., Varon, R., Vega, A., Velasco, A., Vesper, A. -S., Viel, A., Vreeswijk, M. P. G., Wagner, S. A., Waha, A., Walker, L. C., Walters, R. J., Wang-Gohrke, S., Weber, B. H. F., Weichert, W., Wieland, K., Wiesmuller, L., Witzel, I., Wockel, A., Woodward, E. R., Zachariae, S., Zampiga, V., Zeder-Goss, C., Investigators, K., Lazaro, C., De Nicolo, A., Radice, P., Engel, C., Schmutzler, R. K., Goldgar, D. E., Spurdle, A. B., Concolino P., Lucci Cordisco E. (ORCID:0000-0002-6279-7604), Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadalo, L., Aalfs, C. M., Agata, S., Aittomaki, K., Alducci, E., Alonso-Cerezo, M. C., Arnold, N., Auber, B., Austin, R., Azzollini, J., Balmana, J., Barbieri, E., Bartram, C. R., Blanco, A., Blumcke, B., Bonache, S., Bonanni, B., Borg, A., Bortesi, B., Brunet, J., Bruzzone, C., Bucksch, K., Cagnoli, G., Caldes, T., Caliebe, A., Caligo, M. A., Calvello, M., Capone, G. L., Caputo, S. M., Carnevali, I., Carrasco, E., Caux-Moncoutier, V., Cavalli, P., Cini, G., Clarke, E. M., Concolino, Paola, Cops, E. J., Cortesi, L., Couch, F. J., Darder, E., de la Hoya, M., Dean, M., Debatin, I., Del Valle, J., Delnatte, C., Derive, N., Diez, O., Ditsch, N., Domchek, S. M., Dutrannoy, V., Eccles, D. M., Ehrencrona, H., Enders, U., Evans, D. G., Farra, C., Faust, U., Felbor, U., Feroce, I., Fine, M., Foulkes, W. D., Galvao, H. C. R., Gambino, G., Gehrig, A., Gensini, F., Gerdes, A. -M., Germani, A., Giesecke, J., Gismondi, V., Gomez, C., Gomez Garcia, E. B., Gonzalez, S., Grau, E., Grill, S., Gross, E., Guerrieri-Gonzaga, A., Guillaud-Bataille, M., Gutierrez-Enriquez, S., Haaf, T., Hackmann, K., Hansen, T. V. O., Harris, M., Hauke, J., Heinrich, T., Hellebrand, H., Herold, K. N., Honisch, E., Horvath, J., Houdayer, C., Hubbel, V., Iglesias, S., Izquierdo, A., James, P. A., Janssen, L. A. M., Jeschke, U., Kaulfuss, S., Keupp, K., Kiechle, M., Kolbl, A., Krieger, S., Kruse, T. A., Kvist, A., Lalloo, F., Larsen, M., Lattimore, V. L., Lautrup, C., Ledig, S., Leinert, E., Lewis, A. L., Lim, J., Loeffler, M., Lopez-Fernandez, A., Lucci Cordisco, Emanuela, Maass, N., Manoukian, S., Marabelli, M., Matricardi, L., Meindl, A., Michelli, R. D., Moghadasi, S., Moles-Fernandez, A., Montagna, M., Montalban, G., Monteiro, A. N., Montes, E., Mori, L., Moserle, L., Muller, C. R., Mundhenke, C., Naldi, N., Nathanson, K. L., Navarro, M., Nevanlinna, H., Nichols, C. B., Niederacher, D., Nielsen, H. R., Ong, K. -R., Pachter, N., Palmero, E. I., Papi, L., Pedersen, I. S., Peissel, B., Perez-Segura, P., Pfeifer, K., Pineda, M., Pohl-Rescigno, E., Poplawski, N. K., Porfirio, B., Quante, A. S., Ramser, J., Reis, R. M., Revillion, F., Rhiem, K., Riboli, B., Ritter, J., Rivera, D., Rofes, P., Rump, A., Salinas, M., Sanchez de Abajo, A. M., Schmidt, G., Schoenwiese, U., Seggewiss, J., Solanes, A., Steinemann, D., Stiller, M., Stoppa-Lyonnet, D., Sullivan, K. J., Susman, R., Sutter, C., Tavtigian, S. V., Teo, S. H., Teule, A., Thomassen, M., Tibiletti, M. G., Tischkowitz, M., Tognazzo, S., Toland, A. E., Tornero, E., Torngren, T., Torres-Esquius, S., Toss, A., Trainer, A. H., Tucker, K. M., van Asperen, C. J., van Mackelenbergh, M. T., Varesco, L., Vargas-Parra, G., Varon, R., Vega, A., Velasco, A., Vesper, A. -S., Viel, A., Vreeswijk, M. P. G., Wagner, S. A., Waha, A., Walker, L. C., Walters, R. J., Wang-Gohrke, S., Weber, B. H. F., Weichert, W., Wieland, K., Wiesmuller, L., Witzel, I., Wockel, A., Woodward, E. R., Zachariae, S., Zampiga, V., Zeder-Goss, C., Investigators, K., Lazaro, C., De Nicolo, A., Radice, P., Engel, C., Schmutzler, R. K., Goldgar, D. E., Spurdle, A. B., Concolino P., and Lucci Cordisco E. (ORCID:0000-0002-6279-7604)

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

21. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

Author

Blanco, I., Kuchenbaecker, K., Cuadras, D., Wang, X.S., Barrowdale, D., Garibay, G.R., Librado, P., Sanchez-Gracia, A., Rozas, J., Bonifaci, N., McGuffog, L., Pankratz, V.S., Islam, A., Mateo, F., Berenguer, A., Petit, A., Catala, I., Brunet, J., Feliubadalo, L., Tornero, E., Benitez, J., Osorio, A., Cajal, T.R.Y., Nevanlinna, H., Aittomaki, K., Arun, B.K., Toland, A.E., Karlan, B.Y., Walsh, C., Lester, J., Greene, M.H., Mai, P.L., Nussbaum, R.L., Andrulis, I.L., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Barkardottir, R.B., Jakubowska, A., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Claes, K., Maerken, T. van, Diez, O., Hansen, T.V., Jonson, L., Gerdes, A.M., Ejlertsen, B., Hoya, M. de la, Caldees, T., Dunning, A.M., Oliver, C., Fineberg, E., Cook, M., Peock, S., McCann, E., Murray, A., Jacobs, C., Pichert, G., Lalloo, F., Chu, C., Dorkins, H., Paterson, J., Ong, K.R., Teixeira, M.R., Teixeira, Hogervorst, F.B.L., Hout, A.H. van der, Seynaeve, C., Luijt, R.B. van der, Ligtenberg, M.J.L., Devilee, P., Wijnen, J.T., Rookus, M.A., Meijers-Heijboer, H.E.J., Blok, M.J., Ouweland, A.M.W. van den, Aalfs, C.M., Rodriguez, G.C., Phillips, K.A.A., Piedmonte, M., Nerenstone, S.R., Bae-Jump, V.L., O'Malley, D.M., Ratner, E.S., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Plendl, H.J., Niederacher, D., Sutter, C., Wang-Gohrke, S., Steinemann, D., Preisler-Adams, S., Kast, K., Varon-Mateeva, R., Gehrig, A., Bojesen, A., Pedersen, I.S., Sunde, L., Jensen, U.B., Thomassen, M., Kruse, T.A., Foretova, L., Peterlongo, P., Bernard, L., Peissel, B., Scuvera, G., Manoukian, S., Radice, P., Ottini, L., Montagna, M., Agata, S., Maugard, C., Simard, J., Soucy, P., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Geschwantler-Kaulich, D., Tea, M.K., Pfeiler, G., John, E.M., Miron, A., Neuhausen, S.L., Terry, M.B., Chung, W.K., Daly, M.B., Goldgar, D.E., Janavicius, R., Dorfling, C.M., Rensburg, E.J. van, Fostira, F., Konstantopoulou, I., Garber, J., Godwin, A.K., Olah, E., Narod, S.A., Rennert, G., Paluch, S.S., Laitman, Y., Friedman, E., Liljegren, A., Rantala, J., Stenmark-Askmalm, M., Loman, N., Imyanitov, E.N., Hamann, U., Spurdle, A.B., Healey, S., Weitzel, J.N., Herzog, J., Margileth, D., Gorrini, C., Esteller, M., Gomez, A., Sayols, S., Vidal, E., Heyn, H., Stoppa-Lyonnet, Leone, M., Barjhoux, L., Fassy-Colcombet, M., Pauw, A. de, Lasset, C., Ferrer, S.F., Castera, L., Berthet, P., Cornelis, F., Bignon, Y.J., Damiola, F., Mazoyer, S., Sinilnikova, O.M., Maxwell, C.A., Vijai, J., Robson, M., Kauff, N., Corines, M.J., Villano, D., Cunningham, J., Lee, A., Lindor, N., Lazaro, C., Easton, D.F., Offit, K., Chenevix-Trench, G., Couch, F.J., Antoniou, A.C., Pujana, M.A., BCFR, SWE-BRCA, KConFab Investigators, GEMO, Human genetics, CCA - Oncogenesis, Medical Oncology, Clinical Genetics, Suzuki, Hiromu, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Department of Obstetrics and Gynecology, Clinicum, Medicum, Haartman Institute (-2014), and Department of Medical and Clinical Genetics

Subjects
single nucleotide, Oncology, Carcinogenesis, TUBG1, Genes, BRCA2, Genes, BRCA1, Càncer d'ovari, MODIFIERS, Genome-wide association study, Cell Cycle Proteins, Breast cancer, mammary glands, Aetiology, genes, skin and connective tissue diseases, Cancer, Extracellular Matrix Proteins, Hazard ratio, CHIP-SEQ, 3. Good health, ddc, Hyaluronan Receptors, Medicine, Teixeira, Human, medicine.medical_specialty, Evolution, Science, Non-P.H.S, Single-nucleotide polymorphism, Evolution, Molecular, SDG 3 - Good Health and Well-being, Ovarian cancer, Genetics, biochemistry, Humans, human, CELL, Polymorphism, GENOME-WIDE ASSOCIATION, medicine (all), Retrospective Studies, Cancer och onkologi, Prevention, Mutació (Biologia), Biology and Life Sciences, Molecular, SWE-BRCA, BRCA1, medicine.disease, BRCA2, POLYMORPHISM, Genes, Genetic Loci, Cancer and Oncology, Mutation, U.S. Gov't, Bioinformatics, medicine.disease_cause, 3123 Gynaecology and paediatrics, Tubulin, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], ELEMENTS, 2.1 Biological and endogenous factors, CD44, Non-U.S. Gov't, Aurora Kinase A, Likelihood Functions, Multidisciplinary, Research Support, Non-U.S. Gov't, agricultural and biological sciences (all), genetics and molecular biology (all), BCFR, Nuclear Proteins, Single Nucleotide, Mammary Glands, SURVIVAL, kConFab Investigators, Female, Microtubule-Associated Proteins, Research Article, Antigens, CD44, aurora kinase A, breast neoplasms, carcinogenesis, cell cycle proteins, estrogen receptor alpha, evolution, molecular, extracellular matrix proteins, female, genetic loci, genetic predisposition to disease, humans, likelihood functions, mammary glands, human, microtubule-associated proteins, nuclear proteins, polymorphism, retrospective studies, tubulin, genes, BRCA1, genes, BRCA2, mutation, biochemistry, genetics and molecular biology (all), SUSCEPTIBILITY LOCI, General Science & Technology, 3122 Cancers, Breast Neoplasms, Biology, Research Support, Polymorphism, Single Nucleotide, N.I.H, GENETIC INTERACTION NETWORKS, Càncer de mama, EXPRESSION SIGNATURE, Amino acid sequence, Research Support, N.I.H., Extramural, Internal medicine, Seqüència d'aminoàcids, evolution, Genetic variation, Journal Article, medicine, Genetic Predisposition to Disease, ddc:610, molecular, Antigens, Mammary Glands, Human, ddc:611, Intramural, Estrogen Receptor alpha, Extramural, Mutation (Biology), Research Support, N.I.H., Intramural, 3111 Biomedicine, GEMO, Research Support, U.S. Gov't, Non-P.H.S
Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values greater than 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. Funding Agencies|National Cancer Institute [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepajas municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network from the National Cancer Institute and the Office of the Director, National Institutes of Health; Hereditary Cancer Research Registry from the National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Fondazione IRCCS Istituto Nazionale Tumori; Cancer Research-United Kingdom grant [C12292/A11174, C1287/ A10118]; NHMRC Program Grant; DKFZ; European Union (European Social Fund-ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; European Social Fund; Cancer Research United Kingdom Grants [C1287/A10118, C1287/A11990]; National Institute of Health Research (NIHR) grant; NIHR grant; Royal Marsden NHS Foundation Trust; Cancer Research United Kingdom Grant [C5047/A8385]; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; AKG [5U01CA113916, R01CA140323]; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlonsen!" Award; Canadian Institutes of Health Research; Fund for Scientific Research Flanders (FWO); National Cancer Institute grant [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOGs Cancer Prevention and Control Committee [CA 101165]; Intramural Research Program, NCI; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grant [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hungarian Research Grant [KTIA-OTKA CK-80745]; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/OP-9]; Spanish Ministry of Health ISCIII FIS [PI10/01422, PI12/01528, PI13/00285]; RTICC [RD12/0036/0008]; Ramon Areces (XV) Foundation; Eugenio Rodriguez Pascual Foundation; Roses Contra el Cancer Foundation; Spanish Association Against Cancer (AECC); AGAUR Generalitat de Catalunya [2009-SGR290, 2009-SGR293]; Polish Foundation of Science; Icelandic Association "Walking for Breast Cancer Research"; Nordic Cancer Union; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade-grant [PSR-SIIRI-701]; Ministero dellIstruzione, dellUniversita e della Ricerca and Ministero della Salute; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Foundation of Western Australia; Cancer Councils of Tasmania; National Institutes of Health grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; United States Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Jewish General Hospital Weekend; Quebec Ministry of Economic Development, Innovation and Export Trade; Cancer Councils of South Australia; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; MH CZ-DRO (MMCI) [00209805]; Niehaus Family Genetics Research Fund; STARR Cancer Consortium Grant; NAROD [1R01 CA149429-01]; NCI Intramural Research Program, National Institutes of Health [NO2-CP-11019-50, N02-CP-65504]; Westat, Inc, Rockville, Maryland; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant from the National Cancer Institute [UM1 CA164920]; Breast Cancer Family Registry (BCFR); United States Government or the BCFR; Ohio State University Comprehensive Cancer Center; Isreal cancer association; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Womens Cancer Research Alliance; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; SAF2010-20493; [PBZ_KBN_122/P05/2004]

Published
2015
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22. Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

Author

Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, X, Barrowdale, D, De Garibay, GR, Librado, P, Sánchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Català, I, Brunet, J, Feliubadaló, L, Tornero, E, Benítez, J, Osorio, A, Teresa, R, Teresa, C, Nevanlinna, H, Aittomäki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Díez, O, Hansen, TV, Jønson, L, Gerdes, AM, Ejlertsen, B, De La Hoya, M, Caldés, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, T, Hogervorst, FBL, Van Der Hout, AH, Seynaeve, C, Van Der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, Van Den Ouweland, AMW, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, and Wang-Gohrke, S

Subjects
skin and connective tissue diseases
Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4(false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteractionvalues > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Published
2015
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23. Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study

Author

Benito, N., primary, Franco, M., additional, Ribera, A., additional, Soriano, A., additional, Rodriguez-Pardo, D., additional, Sorlí, L., additional, Fresco, G., additional, Fernández-Sampedro, M., additional, Dolores del Toro, M., additional, Guío, L., additional, Sánchez-Rivas, E., additional, Bahamonde, A., additional, Riera, M., additional, Esteban, J., additional, Baraia-Etxaburu, J.M., additional, Martínez-Alvarez, J., additional, Jover-Sáenz, A., additional, Dueñas, C., additional, Ramos, A., additional, Sobrino, B., additional, Euba, G., additional, Morata, L., additional, Pigrau, C., additional, Coll, P., additional, Mur, I., additional, Ariza, J., additional, Barcenilla, F., additional, Pérez-Villar, F., additional, Prats-Gispert, L., additional, Cisterna, R., additional, Ibarra, S., additional, López, Í., additional, Santamaría, J.M., additional, Cabo, J., additional, García, D., additional, Lora-Tamayo, J., additional, Murillo, O., additional, Pedrero, S., additional, Álvarez-Parrondo, S., additional, Muedra-Font, R., additional, Raya-Fernández, C., additional, Rodríguez-Alonso, C., additional, Moreno, A., additional, Blanco-Martínez-de-Morentin, M.A., additional, Cabo-Magadan, R., additional, Combalia, A., additional, García, S., additional, Martínez-Pastor, J.C., additional, Tornero, E., additional, Merino-Pérez, J., additional, Montejo, J.M., additional, Alier, A., additional, Horcajada, J.P., additional, Plasencia, V., additional, Puig, L., additional, Auñon, Á., additional, Blanco, A., additional, García-Cañete, J., additional, Sandoval, E., additional, Fakkas-Fernández, M., additional, Garcés-Zarzalejo, C., additional, Fariñas-Alvarez, C., additional, Fariñas, M.C., additional, Martinez-Martinez, L., additional, Salas-Venero, C., additional, Cobo, J., additional, Ruiz-Carbajosa, P., additional, Jordán, M., additional, Crusi, X., additional, Marinescu, C., additional, Montaner, F., additional, Ramírez, A., additional, Corona, P.S., additional, Lung, M., additional, Muniain-Ezcurra, M.Á., additional, Peñas-Espinar, C., additional, Suárez, A.I., additional, Álvarez, R., additional, Cordero, J.-A., additional, López-Pliego, M., additional, Palomino, J., additional, and Puente, A., additional

Published
2016
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25. Identification of a founderBRCA1mutation in the Moroccan population

Author

Quiles, F., primary, Teulé, À., additional, Martinussen Tandstad, N., additional, Feliubadaló, L., additional, Tornero, E., additional, del Valle, J., additional, Menéndez, M., additional, Salinas, M., additional, Wethe Rognlien, V., additional, Velasco, A., additional, Izquierdo, A., additional, Capellá, G., additional, Brunet, J., additional, and Lázaro, C., additional

Published
2016
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26. Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

Author

Blanco, I. (Ignacio), Kuchenbaecker, K.B. (Karoline), Cuadras, D. (Daniel), Wang, X. (Xing), Barrowdale, D. (Daniel), De Garibay, G.R. (Gorka Ruiz), Librado, P. (Pablo), Sánchez-Gracia, A. (Alejandro), Rozas, J. (Julio), Bonifaci, N. (Núria), McGuffog, L. (Lesley), Pankratz, V.S. (Shane), Islam, A.B.M.M.K. (Abul), Mateo, F. (Francesca), Berenguer, A. (Antonio), Petit, A. (Anna), Català, I. (Isabel), Brunet, J. (Joan), Feliubadaló, L. (L.), Tornero, E. (Eva), Benítez, J. (Javier), Osorio, A. (Ana), Teresa, R. (Ramón), Teresa, C. (Cajal), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Arun, B.K. (Banu), Toland, A.E. (Amanda), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Greene, M.H. (Mark), Mai, P.L. (Phuong), Nussbaum, R.L. (Robert L.), Andrulis, I.L. (Irene), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Barkardottir, R.B. (Rosa), Jakubowska, A. (Anna), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Claes, K. (Kathleen), Van Maerken, T. (Tom), Díez, O. (Orland), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Dunning, A.M. (Alison), Oliver, C.T. (Clare), Fineberg, E. (Elena), Cook, M. (Margaret), Peock, S. (Susan), McCann, E. (Emma), Murray, A. (Alexandra), Jacobs, C. (Chris), Pichert, G. (Gabriella), Lalloo, F. (Fiona), Chu, C. (Carol), Dorkins, H. (Huw), Paterson, J. (Joan), Ong, K.-R. (Kai-Ren), Teixeira, M.R. (Manuel R.), Teixeira, T. (T.), Hogervorst, F.B.L. (Frans), Hout, A.H. (Annemarie) van der, Seynaeve, C.M. (Caroline), Van Der Luijt, R.B. (Rob B.), Ligtenberg, M.J. (Marjolijn), Devilee, P. (Peter), Wijnen, J.T. (Juul), Rookus, M.A. (Matti), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Ouweland, A.M.W. (Ans) van den, Aalfs, C.M. (Cora), Rodriguez, G.C. (Gustavo C.), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Nerenstone, S. (Stacy), Bae-Jump, V.L. (Victoria L.), O'Malley, D.M. (David M.), Ratner, E.S. (Elena S.), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Jensen, U.B., Thomassen, M. (Mads), Kruse, T.A. (Torben), Foretova, L. (Lenka), Peterlongo, P. (Paolo), Bernard, L. (Loris), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Radice, P. (Paolo), Ottini, L. (Laura), Montagna, M. (Marco), Agata, S. (Simona), Maugard, C., Simard, J. (Jacques), Soucy, P. (Penny), Berger, A. (Annemarie), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Tea, M.-K., Pfeiler, G. (Georg), John, E.M. (Esther), Miron, A. (Alexander), Neuhausen, S.L. (Susan), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Daly, M.B. (Mary), Goldgar, D. (David), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J., Godwin, A.K. (Andrew), Olah, E., Narod, S.A. (Steven A.), Rennert, G. (Gad), Paluch, S.S. (Shani), Laitman, Y. (Yael), Friedman, E. (Eitan), Liljegren, A. (Annelie), Rantala, J. (Johanna), Stenmark-Askmalm, M. (Marie), Loman, N. (Niklas), Imyanitov, E.N. (Evgeny), Hamann, U. (Ute), Spurdle, A.B. (Amanda), Healey, S. (Sue), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Margileth, D. (David), Gorrini, C. (Chiara), Esteller, M. (Manel), Gómez, A. (Antonio), Sayols, S. (Sergi), Vidal, E. (Enrique), Heyn, H. (Holger), Stoppa-Lyonnet, D. (Dominique), Léone, M. (Mélanie), Barjhoux, L. (Laure), Fassy-Colcombet, M. (Marion), Pauw, A. (Antoine) de, Lasset, C. (Christine), Ferrer, S.F., Castera, L. (Laurent), Berthet, P. (Pascaline), Cornelis, F. (Franco̧is), Bignon, Y.-J. (Yves-Jean), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Maxwell, C.A. (Christopher), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Corines, M.J. (Marina J.), Villano, D. (Danylko), Cunningham, J.M. (Julie), Lee, A. (Adam), Lindor, N.M. (Noralane), Lázaro, C. (Conxi), Easton, D.F. (Douglas), Offit, K. (Kenneth), Chenevix-Trench, G. (Georgia), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis C.), Pujana, M.A. (Miguel), Blanco, I. (Ignacio), Kuchenbaecker, K.B. (Karoline), Cuadras, D. (Daniel), Wang, X. (Xing), Barrowdale, D. (Daniel), De Garibay, G.R. (Gorka Ruiz), Librado, P. (Pablo), Sánchez-Gracia, A. (Alejandro), Rozas, J. (Julio), Bonifaci, N. (Núria), McGuffog, L. (Lesley), Pankratz, V.S. (Shane), Islam, A.B.M.M.K. (Abul), Mateo, F. (Francesca), Berenguer, A. (Antonio), Petit, A. (Anna), Català, I. (Isabel), Brunet, J. (Joan), Feliubadaló, L. (L.), Tornero, E. (Eva), Benítez, J. (Javier), Osorio, A. (Ana), Teresa, R. (Ramón), Teresa, C. (Cajal), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Arun, B.K. (Banu), Toland, A.E. (Amanda), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Greene, M.H. (Mark), Mai, P.L. (Phuong), Nussbaum, R.L. (Robert L.), Andrulis, I.L. (Irene), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Barkardottir, R.B. (Rosa), Jakubowska, A. (Anna), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Claes, K. (Kathleen), Van Maerken, T. (Tom), Díez, O. (Orland), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Dunning, A.M. (Alison), Oliver, C.T. (Clare), Fineberg, E. (Elena), Cook, M. (Margaret), Peock, S. (Susan), McCann, E. (Emma), Murray, A. (Alexandra), Jacobs, C. (Chris), Pichert, G. (Gabriella), Lalloo, F. (Fiona), Chu, C. (Carol), Dorkins, H. (Huw), Paterson, J. (Joan), Ong, K.-R. (Kai-Ren), Teixeira, M.R. (Manuel R.), Teixeira, T. (T.), Hogervorst, F.B.L. (Frans), Hout, A.H. (Annemarie) van der, Seynaeve, C.M. (Caroline), Van Der Luijt, R.B. (Rob B.), Ligtenberg, M.J. (Marjolijn), Devilee, P. (Peter), Wijnen, J.T. (Juul), Rookus, M.A. (Matti), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Ouweland, A.M.W. (Ans) van den, Aalfs, C.M. (Cora), Rodriguez, G.C. (Gustavo C.), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Nerenstone, S. (Stacy), Bae-Jump, V.L. (Victoria L.), O'Malley, D.M. (David M.), Ratner, E.S. (Elena S.), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Jensen, U.B., Thomassen, M. (Mads), Kruse, T.A. (Torben), Foretova, L. (Lenka), Peterlongo, P. (Paolo), Bernard, L. (Loris), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Radice, P. (Paolo), Ottini, L. (Laura), Montagna, M. (Marco), Agata, S. (Simona), Maugard, C., Simard, J. (Jacques), Soucy, P. (Penny), Berger, A. (Annemarie), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Tea, M.-K., Pfeiler, G. (Georg), John, E.M. (Esther), Miron, A. (Alexander), Neuhausen, S.L. (Susan), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Daly, M.B. (Mary), Goldgar, D. (David), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J., Godwin, A.K. (Andrew), Olah, E., Narod, S.A. (Steven A.), Rennert, G. (Gad), Paluch, S.S. (Shani), Laitman, Y. (Yael), Friedman, E. (Eitan), Liljegren, A. (Annelie), Rantala, J. (Johanna), Stenmark-Askmalm, M. (Marie), Loman, N. (Niklas), Imyanitov, E.N. (Evgeny), Hamann, U. (Ute), Spurdle, A.B. (Amanda), Healey, S. (Sue), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Margileth, D. (David), Gorrini, C. (Chiara), Esteller, M. (Manel), Gómez, A. (Antonio), Sayols, S. (Sergi), Vidal, E. (Enrique), Heyn, H. (Holger), Stoppa-Lyonnet, D. (Dominique), Léone, M. (Mélanie), Barjhoux, L. (Laure), Fassy-Colcombet, M. (Marion), Pauw, A. (Antoine) de, Lasset, C. (Christine), Ferrer, S.F., Castera, L. (Laurent), Berthet, P. (Pascaline), Cornelis, F. (Franco̧is), Bignon, Y.-J. (Yves-Jean), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Maxwell, C.A. (Christopher), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Corines, M.J. (Marina J.), Villano, D. (Danylko), Cunningham, J.M. (Julie), Lee, A. (Adam), Lindor, N.M. (Noralane), Lázaro, C. (Conxi), Easton, D.F. (Douglas), Offit, K. (Kenneth), Chenevix-Trench, G. (Georgia), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis C.), and Pujana, M.A. (Miguel)

Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appro

Published
2015
Full Text
View/download PDF

27. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

Author

Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, XS, Barrowdale, D, Garibay, GR, Librado, P, Sanchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Catala, I, Brunet, J, Feliubadalo, L, Tornero, E, Benitez, J, Osorio, A, Cajal, TRY, Nevanlinna, H, Aittomaki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Diez, O, Hansen, TV, Jonson, L, Gerdes, AM, Ejlertsen, B, de la Hoya, M, Caldees, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, Hogervorst, FBL, van der Hout, AH, Seynaeve, Caroline, van der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, van den Ouweland, Ans, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, Marga, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gomez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, Leone, M, Barjhoux, L, Fassy-Colcombet, M, de Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, van der Lee, A, Lindor, N, Lazaro, C (Conxi), Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC, Pujana, MA, Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, XS, Barrowdale, D, Garibay, GR, Librado, P, Sanchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Catala, I, Brunet, J, Feliubadalo, L, Tornero, E, Benitez, J, Osorio, A, Cajal, TRY, Nevanlinna, H, Aittomaki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Diez, O, Hansen, TV, Jonson, L, Gerdes, AM, Ejlertsen, B, de la Hoya, M, Caldees, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, Hogervorst, FBL, van der Hout, AH, Seynaeve, Caroline, van der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, van den Ouweland, Ans, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, Marga, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gomez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, Leone, M, Barjhoux, L, Fassy-Colcombet, M, de Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, van der Lee, A, Lindor, N, Lazaro, C (Conxi), Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC, and Pujana, MA

Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Published
2015

30. FRI0408 Analysis of Disease Activity and Response to Treatment in A Large Cohort from the Spanish Society of Rheumatology Registry of Patients with Systemic Lupus Erythematosus (RELESSER)

Author

Pego-Reigosa, J.M., primary, Rúa, I., additional, del Campo, V., additional, García-Yébenes, M.J., additional, Lόpez-Longo, F.J., additional, Galindo, M., additional, Calvo, J., additional, Loza, E., additional, Olivé, A., additional, Blanco, R., additional, Vela, P., additional, Rodríguez, M., additional, Mouriño, C., additional, Oton, T., additional, Tornero, E., additional, Uriarte, E., additional, Freire, M., additional, Fito, C., additional, Fernández-Nebro, A., additional, Narvaez, J., additional, Zea, A., additional, Rosas, J.C., additional, Hernández, J.A., additional, Hernández, B., additional, Sánchez, A., additional, Ibáñez, M., additional, and Pérez-Venegas, J.J., additional

Published
2014
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31. Identification of a founder BRCA1 mutation in the Moroccan population.

Author

Quiles, F., Teulé, À., Martinussen Tandstad, N., Feliubadaló, L., Tornero, E., Valle, J., Menéndez, M., Salinas, M., Wethe Rognlien, V., Velasco, A., Izquierdo, A., Capellá, G., Brunet, J., and Lázaro, C.

Subjects
BRCA genes, MUTAGENESIS, FOUNDER effect, BREAST cancer patients, GENETICS of disease susceptibility, PUBLIC health
Abstract

Breast cancer ( BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC-predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high-risk families identified mutation BRCA1 c. 5309G>T, p.( Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population. [ABSTRACT FROM AUTHOR]

Published
2016
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32. Reseñas

Author

Mediano, F. R., Kuhn, R., García-Arenal, M., Tornero, E., Ávila, M. L., Lucini, M., Marín, M., Garulo, T., Fierro, M., and El Hour, R.

Published
1997
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34. NIRS potential use for the determination of natural resources quality from dehesa (acorn and grass) in Montanera system for Iberian pigs.

Author

Tejerina, D., García-Torres, S., Martín-Tornero, E., Gordillo, A., Ortiz, A., Ferraz-de-Oliveira, M. I., Machado, G., Sales-Baptista, E., Cabeza de Vaca, M., and Romero-Fernández, M. P.

Subjects
MEAT quality, SWINE nutrition, NEAR infrared spectroscopy
Abstract

Copyright of Archivos de Zootecnia is the property of Archivos de Zootecnia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2018

35. [The construction and validation of a questionnaire on the satisfaction of primary health care users]

Author

Jm, Pérez Moreno, Otero A, Pérez Tornero E, Parron T, Bretones C, and Je, Sánchez Romero

Subjects
Observer Variation, Primary Health Care, Spain, Surveys and Questionnaires, Humans, Reproducibility of Results, Consumer Behavior, Epidemiologic Methods, Quality of Health Care
Abstract

The questionnaire was developed after establishing the domains that might be measured with it and selecting 16 items. During June and September 1987 it was administered to 163 patients, selected by quota sampling, who belonged to two health centers and two outpatient clinics from the city of Almería. With the obtained data several parts of the questionnaire were validated: stability, homogeneity, distorting variables and constructed validity. There were significant differences (analysis of variance) between the satisfaction of the users of health centers and outpatient clinics (p = 0.042) (higher satisfaction in health centers). There were not marked differences between the users of both health centers (p = 0.144) and between both outpatient clinics (p = 0.66). The measurement of satisfaction is a valuable instrument for the investigation and administration of health services and a good indicator of the quality of care.

Published
1989

39. TREATMENT CHANGE IN ADOLESCENTS WITH SOCIAL ANXIETY DISORDER: INSIGHTS FROM CORPUS LINGUISTICS.

Author

J. Garcia-Lopez, L., B. Díez-Bedmar, M., Pérez-Paredes, P., and Tornero, E.

Subjects
*SOCIAL anxiety, *ANXIETY in adolescence, *TREATMENT effectiveness, *CORPORA, *PSYCHOLINGUISTICS, *SOCIAL psychology, *THERAPEUTICS
Abstract

Despite the efforts made in Clinical Psychology, the remission rates of social anxiety disorder are still moderate, which might stem from a lack of sensitivity in the psychological treatment outcome measures. New interdisciplinary perspectives such as the joint efforts of Corpus Linguistics and Psychology are, therefore, being sought. The purpose of this study is to explore if the linguistic insights provided by Corpus Linguistics are of any help when assessing sensitivity on treatment in adolescents with generalized social anxiety disorder. Results revealed the relevance of analysing adolescents' written texts for treatment outcome analysis by examining adolescents' texts based on the triple-response-system approach (cognitive, somatic and behavioural symptoms) and the DSM criteria for social anxiety disorder. The findings of this interdisciplinary paper are consistent with the DSM-V criteria in the proposed revision for social anxiety disorder. [ABSTRACT FROM AUTHOR]

Published
2011

40. TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.

Author

Rofes P, Castillo-Manzano C, Menéndez M, Teulé Á, Iglesias S, Munté E, Ramos-Muntada M, Gómez C, Tornero E, Darder E, Montes E, Valle L, Capellá G, Pineda M, Brunet J, Feliubadaló L, Del Valle J, and Lázaro C

Subjects
Humans, Female, Male, Adult, Middle Aged, Adolescent, Young Adult, Tumor Suppressor Protein p53 genetics, Germ-Line Mutation, Li-Fraumeni Syndrome genetics, Li-Fraumeni Syndrome diagnosis, Genetic Predisposition to Disease, Genetic Testing methods
Abstract

Background: Germline heterozygous pathogenic variants (PVs) in TP53 cause Li-Fraumeni syndrome (LFS), a condition associated with increased risk of multiple tumor types. As the associated cancer risks were refined over time, clinical criteria also evolved to optimize diagnostic yield. The implementation of multi-gene panel germline testing in different clinical settings has led to the identification of TP53 PV carriers outside the classic LFS-associated cancer phenotypes, leading to a broader cancer phenotypic redefinition and to the renaming of the condition as "heritable TP53-related cancer syndrome" (hTP53rc). Germline TP53 variant interpretation is challenging due to the diverse nature of TP53 PVs, variable penetrance of the syndrome, possible occurrence of TP53 somatic mosaicism, and TP53 involvement in clonal hematopoiesis of indeterminate potential (CHIP). Here we aim to assess the relevance and impact of these issues on the diagnostic routine, and to evaluate the sensitivity of the different LFS clinical criteria to identify hTP53rc., Methods: TP53 was analyzed in 6161 suspected hereditary cancer non-related patients categorized into three subgroups: (1) 495 patients fulfilling any LFS/Chompret clinical criteria; (2) 2481 patients diagnosed with early-onset breast/colorectal cancer; (3) 3185 patients without clinical criteria suggestive of hTP53rc. Ancillary tests were performed when TP53 PVs were identified in individuals not meeting LFS/Chompret criteria and/or when the variant was identified at low variant allele frequency (VAF)., Results: TP53 PVs were identified in blood DNA of 45 probands. Variant origin was elucidated in 39 of these: 72% patients had a constitutional PV, 10% were mosaics, and 18% had CHIP-associated PVs. Notably, two of the seven CHIP-TP53 PVs identified were detected at high allelic frequencies (VAF > 35%). Twenty-nine percent of germline TP53 PV did not meet any of the LFS clinical criteria. Among the clinical criteria, Chompret 2009 showed the highest sensitivity in our cohort (68% vs. 54% for Chompret 2015), highlighting the relevance of considering lung cancer in the criteria., Conclusions: Our data supports performing TP53 ancillary testing for the identification of potential mosaicisms and CHIP-associated PVs, particularly in patients not meeting clinical criterial for LFS, irrespective of the VAF, and the application of clinical criteria that include lung cancer diagnosis., Competing Interests: Declarations. Ethics approval and consent to participate: The research was conducted in accordance with the principles of the Declaration of Helsinki, and ethical approval was obtained from the ethics committee of Bellvitge Biomedical Research Institute (IDIBELL; PR278/19). Informed written consent for both diagnostic and research purposes was obtained from all participants. Consent for publication: Written informed consent for publication was obtained from all study participants. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Published
2025
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41. vaRHC: an R package for semi-automation of variant classification in hereditary cancer genes according to ACMG/AMP and gene-specific ClinGen guidelines.

Author

Munté E, Feliubadaló L, Pineda M, Tornero E, Gonzalez M, Moreno-Cabrera JM, Roca C, Bales Rubio J, Arnaldo L, Capellá G, Mosquera JL, and Lázaro C

Subjects
Humans, United States, Genetic Testing, Genetic Predisposition to Disease, Bayes Theorem, Genome, Human, Automation, Genetic Variation, Neoplasms genetics
Abstract

Motivation: Germline variant classification allows accurate genetic diagnosis and risk assessment. However, it is a tedious iterative process integrating information from several sources and types of evidence. It should follow gene-specific (if available) or general updated international guidelines. Thus, it is the main burden of the incorporation of next-generation sequencing into the clinical setting., Results: We created the vaRiants in HC (vaRHC) R package to assist the process of variant classification in hereditary cancer by: (i) collecting information from diverse databases; (ii) assigning or denying different types of evidence according to updated American College of Molecular Genetics and Genomics/Association of Molecular Pathologist gene-specific criteria for ATM, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, PTEN, and TP53 and general criteria for other genes; (iii) providing an automated classification of variants using a Bayesian metastructure and considering CanVIG-UK recommendations; and (iv) optionally printing the output to an .xlsx file. A validation using 659 classified variants demonstrated the robustness of vaRHC, presenting a better criteria assignment than Cancer SIGVAR, an available similar tool., Availability and Implementation: The source code can be consulted in the GitHub repository (https://github.com/emunte/vaRHC) Additionally, it will be submitted to CRAN soon., (© The Author(s) 2023. Published by Oxford University Press.)

Published
2023
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42. Can the intra-operative measurement of the diameter of the femoral head help surgeons to choose the best size of the acetabular cup?

Author

Muñoz-Mahamud E, Chimeno C, Tornero E, Alías A, Fernández-Valencia JÁ, and Combalia A

Subjects
Humans, Femur Head surgery, Acetabulum diagnostic imaging, Acetabulum surgery, Femur, Arthroplasty, Replacement, Hip adverse effects, Surgeons
Abstract

Purpose: We hypothesized that the intra-operative measurement of the femoral head may increase the accuracy of the acetabular cup size optimal selection in total hip arthroplasty (THA). The purpose of this clinical research was to analyze the correlation between the estimated cup size from intra-operative measurement of the femoral head and the pre-operative templated cup size., Methods: A prospective observational single-center study was conducted from June 2019 to January 2020 including primary THA (n = 100). All cases were pre-operatively templated. The measurement of the anterior-posterior diameter of the femoral head was routinely intra-operatively performed. Any definitive implanted cup was considered as "oversized" when the size was > 4 mm than the diameter of the native head., Results: The median (interquartile range) size of the implanted cup, pre-operative planned cup size, and diameter of the femoral head were measured 52 (50-54) mm, 50 (48-54) mm and 49 (45-51) mm, respectively. Pre-operative planned size cup accurately predicted the implanted cup or differed in only one size (2 mm) in 77 (78%) cases. Otherwise, intra-operative femoral head measurement method accurately predicted the implanted or differed in only one size (2 mm) in 51 (87%) cases (p = 0.097)., Conclusion: The intra-operative femoral head measurement is a simple and reliable tool to help the surgeons choose the best size of the acetabular cup and is as reliable as the pre-operative templating in order to avoid cup oversizing in THA. Utmost caution is warranted whenever the cup reamer is > 4 mm than the anterior-posterior diameter of the native head., (© 2022. The Author(s).)

Published
2022
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43. Fluorescence Monitoring Oxidation of Extra Virgin Olive Oil Packed in Different Containers.

Author

Martín-Tornero E, Fernández A, Durán-Merás I, and Martín-Vertedor D

Subjects
Olive Oil chemistry, Oxidation-Reduction, Least-Squares Analysis, Spectrometry, Fluorescence methods, Multivariate Analysis, Plant Oils chemistry
Abstract

'Picual' olive oil was stored in different types of containers for 10 months and monitored via quality parameters. In combination with the mentioned analysis, non-destructive fluorescence spectroscopy was performed combined with multivariate analysis to monitor and quantify oil quality levels. Excitation emission matrices (EMMs) were analyzed using parallel factor analysis (PARAFAC). According to the quality parameters, it was observed that Transparent Crystal (TC) and Opaque Crystal (OC) samples were the ones that deteriorated faster due to their higher exposure to light in comparison with Plastic (P) and Canned (C) samples. In a fast and non-destructive manner, the fluorescence spectroscopy-based prototype successfully monitored the oxidation changes in the EVOOs. Unfolded partial least squares (U-PLS) was used to generate a regression model to quantify quality parameters. Good correlation coefficients were found for the peroxide index, K 232 and the oxidative stability index (r 2 between 0.90 and 0.94 for cross-validation and validation). For all of that, the results obtained confirmed the ability of fluorescence spectroscopy to monitor the quality of olive oil and EEMs combined with U-PLS can be used to analyze these parameters, eluding the classical methods.

Published
2022
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44. Clinical and Radiological Outcome in a Series of Patients Treated by Anterior Cervical Discectomy and Fusion: Retrospective Controlled Study With 2 Different Stand-Alone Cages.

Author

Poblete J, Martinez-Anda JJ, Rebollar-Mendoza AA, Castro-Moreno Y, Torne R, Reyes L, Fuster S, Tornero E, Arch-Tirado E, Leo-Vargas R, Combalia A, and Enseñat J

Abstract

Background: Cervical spine balance and alignment targets after cervical spine surgery are poorly established in patients with cervical spine degenerative disease surgically treated by anterior cervical discectomy and fusion (ACDF). The objective of the study is to determine the correlation between radiological and clinical outcomes in patients surgically treated by ACDF with 2 different stand-alone cervical cages., Methods: Clinical outcomes were evaluated using visual analog scale (VAS), Neck Disability Index (NDI), Nurick Scale, and Japanese Orthopedic Association score for myelopathy. Radiological evaluation included cervical and segmental Cobb angles, cervical sagittal vertical axis (cSVA), T1 slope (T1s), C0-C2 angle, fusion rates, adjacent segment degeneration, and cage subsidence., Results: A total of 80 patients were included with an average age of 53 years. There was a statistically significant improvement in both clinical and radiological evaluations. There was a statistical significant correlation between cervical pain on cervical VAS and cSVA. There was a significant correlation between postoperative T1s and cSVA, related to the improvement in cervical angles. There was no significant difference in rates of fusion, adjacent segment changes, or reoperation between both cervical cages, and there was a higher rate of subsidence in the Aleutian group. There were significant differences between both groups on postoperative NDI and VAS, but this difference is not maintained during follow-up., Conclusions: Cervical sagittal balance is directly related to clinical outcome in patients with cervical spine degenerative disease. Both cervical implants analyzed were comparable in clinical and radiological outcomes., Clinical Relevance: There are important clinical and radiological parameters that should be taken into account for the analysis of the surgical outcome of patients treated by ACDF; this is one of the few studies that report the results with 2 different cervical cage designs., Competing Interests: Declaration of Conflicting Interests: The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2022 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Published
2022
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45. Application of Digital Olfaction for Table Olive Industry.

Author

Sánchez R, Fernández A, Martín-Tornero E, Meléndez F, Lozano J, and Martín-Vertedor D

Subjects
Fermentation, Food Microbiology, Smell, Taste, Olea chemistry
Abstract

The International Olive Council (IOC) established that olives must be free of odors, off-flavors, and absent of abnormal ongoing alterations or fermentations. The use of electronic devices could help when classifying defects in a fast, non-destructive, cheap, and environmentally friendly way. For all of that, table olives were evaluated according to IOC regulation in order to classify the defect predominant perceiving (DPP) of the table olives and their intensity. Abnormal fermentation defects of Spanish-style table olives were assessed previously by an IOC-validated tasting panel. 'Zapateria', 'Putrid', and 'Butyric' were the defects found at different concentrations. Different volatile compounds were identified by gas chromatography in altered table olives. The same samples were measured with an electronic nose device (E-nose). E-nose data combined with chemometrics algorithms, such as PCA and PLS-DA, were able to successfully discriminate between healthy and non-healthy table olives, being this last one also separated between the first and second categories. Volatile compounds obtained with gas chromatography could be related to the E-nose measuring and sensory analysis, being capable of matching the different defects with their correspondents' volatile compounds.

Published
2022
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46. Dynamic Fixation Techniques for the Prevention of Adjacent Segment Disease: A Retrospective Controlled Study.

Author

Fuster S, Martínez-Anda JJ, Castillo-Rivera SA, Vargas-Reverón C, and Tornero E

Abstract

Study Design: Retrospective, controlled study., Purpose: Dynamic fixation (topping-off technique) adjacent to a transforaminal lumbar interbody fusion (TLIF) level was developed to reduce the risk of adjacent segment disease (ASDi). This study was designed to compare the clinical and radiological outcomes between patients who underwent circumferential lumbar fusion (CLF) without the topping-off technique, CLF with dynamic rod constructs (DRC), and CLF with interspinous device (ISD)., Overview of Literature: Lumbar fusion can result in the re-distribution of stress, increased mobility, and increased intradiscal pressure at adjacent levels, ultimately leading to adjacent segment degeneration (ASDe) and ASDi. Dynamic fixation techniques (topping-off techniques) adjacent to vertebral fusion have been developed to reduce the risk of ASDe and ASDi because they provide a transitional zone between a caudal rigid fused segment and cephalad-mobile unfused levels., Methods: A single-center, retrospective, controlled study was designed, including all patients who underwent CLF due to degenerative lumbar spinal disease in Hospital Clinic of Barcelona between 2012 and 2018. Three groups of patients were evaluated as per the type of topping-off technique used: CLF alone group, DRC group, and ISD group. Clinical and radiological outcomes were evaluated., Results: A total of 117 patients were enrolled in the study. Sixty patients (51.3%) underwent CLF without dynamic stabilization, 24 (20.5%) were treated with DRC as topping-off technique, and 33 (28.5%) were treated with an ISD. A total of 12 patients (20.0%) in the CLF alone group showed ASDi at the final follow-up, compared to 1 (4.2%) in the DRC group (p=0.097) and 2 (6.1%) in the ISD group (p=0.127). The Cox regression model identified a significantly decreased risk of ASDi when a topping-off technique (DRC or ISD) was used (hazard ratio, 0.154; 95% confidence interval, 0.31-0.77)., Conclusions: Dynamic fixation adjacent to CLF was a safe and efficient procedure associated with improved clinical outcomes in patients with lumbar spine degenerative disease.

Published
2022
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47. Usefulness of serum D-dimer and platelet count to mean platelet volume ratio to rule out chronic periprosthetic joint infection.

Author

Muñoz-Mahamud E, Tornero E, Estrada JA, Fernández-Valencia JA, Martínez-Pastor JC, and Soriano Á

Abstract

Background : Diagnosing periprosthetic joint infection (PJI) is challenging and usually requires the evaluation of several biomarkers. Our main aim was to evaluate the usefulness of D-dimer levels as well as the platelet count (PC) to mean platelet volume (MPV) ratio serum as biomarkers to rule out chronic knee and hip infection. Methods : The study enrolled a prospective cohort of 93 patients undergoing hip or knee revision. D-dimer values, PC to MPV ratio, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were preoperatively determined and evaluated as a predictor of PJI. The definitive diagnosis of PJI was established according to the 2018 International Consensus Meeting criteria. Results : A total of 24 (25.8 %) cases were postoperatively diagnosed with PJI. The median D-dimer value was significantly higher ( p   <  0.001) for patients with PJI (1950 ng mL - 1 ) than for patients with aseptic failure (700 ng mL - 1 ). The area under the receiver operating characteristic curves for D-dimer, CRP and ESR was 0.820, 0.793 and 0.791 respectively. D-dimer  ≥  950 ng mL - 1 (91 % sensitivity, 64 % specificity), CRP  ≥  1.95 mg dL - 1 (61 % sensitivity, 90 % specificity) and ESR  >  20 (74 % sensitivity, 82 % specificity) were identified as the values with the best balance between sensitivity and specificity. The mean PC to MPV ratio was 37.0 for PJI patients and 29.8 for patients in the aseptic revision cohort ( p = 0 .067). Conclusions : Serum D-dimer levels appear very unlikely to remain normal in the presence of chronic PJI. The 91 % sensitivity when considering 950 ng mL - 1 as the threshold highlights D-dimer as the most accurate initial test to rule out chronic PJI. Conversely, the PC to MPV ratio may be of limited value for accurately diagnosing PJI., Competing Interests: The contact author has declared that neither they nor their co-authors have any competing interests., (Copyright: © 2022 Ernesto Muñoz-Mahamud et al.)

Published
2022
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48. Electronic nose application for the discrimination of sterilization treatments applied to Californian-style black olive varieties.

Author

Sánchez R, Martín-Tornero E, Lozano J, Fernández A, Arroyo P, Meléndez F, and Martín-Vertedor D

Subjects
Least-Squares Analysis, Olive Oil analysis, Sterilization, Electronic Nose, Olea
Abstract

Background: Olive oil continues to be the main destination for olives. The production of table olives is increasing. 'Californian-style' processes are among the most frequently employed to produce oxidized olives. Sensory evaluation requires the development of an instrumental detection method that can be used as an adjunct to traditional tasting panels., Results: An electronic nose (E-nose) was used to classify two varieties of olives following exposure to different sterilization. Principal component analysis (PCA) revealed that both varieties had different volatile profiles. Sensory panel evaluations were similar for both. Partial least squares-discriminant analysis (PLS-DA) obtained from the E-nose was able to separate the two varieties and explained 82% of total variance. Moreover, volatile profiles correctly classified olives according to sterilization times recorded up to 121 °C . The only exception was at F 0  ≥ 22 min, at which a plot of PCA outcomes failed to differentiate scores. E-nose data showed similar results to those produced from the volatile analysis when grouping samples were sterilized to F 0  ≥ 18 min, at the same time distinguishing these samples from those subjected to less intense thermal treatments. A partial least squares (PLS) chemometric approach was evaluated for quantifying important olive quality parameters. With regards to validation parameters, R P 2 pertaining to perceived defect was 0.88, whilst R P 2 pertaining to overall assessment was 0.78., Conclusions: E-nose offers a fast, inexpensive and non-destructive method for discriminating between varieties and thermal treatments up to a point at which cooking defects are highly similar (from F 0  = 18 onwards). © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Published
2022
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49. Characterization of Polyphenol and Volatile Fractions of Californian-Style Black Olives and Innovative Application of E-nose for Acrylamide Determination.

Author

Martín-Tornero E, Sánchez R, Lozano J, Martínez M, Arroyo P, and Martín-Vertedor D

Abstract

Californian-style black olives require a sterilization treatment that produces a carcinogenic contaminant, acrylamide. Thus, this compound was evaluated in two different olive cultivars using an electronic nose (E-nose). The sterilization intensity had a significant influence on the final phenol concentrations, acrylamide content, and volatile compounds. Increasing the sterilization intensity from 10 to 26 min (F0) reduced the phenol content, but it promoted acrylamide synthesis, leading to a wide range of this toxic substance. The Ester and phenol groups of volatile compounds decreased their content when the sterilization treatment increased; however, aldehyde and other volatile compound groups significantly increased their contents according to the thermal treatments. The compounds 4-ethenyl-pyridine, benzaldehyde, and 2,4-dimethyl-hexane are volatile compounds with unpleasant odours and demonstrated a high amount of influence on the differences found after the application of the thermal treatments. The "Manzanilla Cacereña" variety presented the highest amount of phenolic compounds and the lowest acrylamide content. Finally, it was found that acrylamide content is correlated with volatile compounds, which was determined using multiple linear regression analysis ( R 2 = 0.9994). Furthermore, the aroma of table olives was analysed using an E-nose, and these results combined with Partial Least Square (PLS) were shown to be an accurate method (range to error ratio (RER) >10 and ratio of performance to deviation (RPD) >2.5) for the indirect quantification of this toxic substance.

Published
2021
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50. E-Nose Discrimination of Abnormal Fermentations in Spanish-Style Green Olives.

Author

Sánchez R, Martín-Tornero E, Lozano J, Boselli E, Arroyo P, Meléndez F, and Martín-Vertedor D

Subjects
Humans, Spain, Electronic Nose, Fermentation, Olea metabolism
Abstract

Current legislation in Spain indicates that table olives must be free of off-odors and off-flavors and without symptoms of ongoing alteration or abnormal fermentations. In this regard, the International Olive Council (IOC) has developed a protocol for the sensory classification of table olives according to the intensity of the predominantly perceived defect (PPD). An electronic nose (e-nose) was used to assess the abnormal fermentation defects of Spanish-style table olives that were previously classified by a tasting panel according to the IOC protocol, namely zapateria, butyric, putrid, and musty or humidity. When olives with different defects were mixed, the putrid defect had the greatest sensory impact on the others, while the butyric defect had the least sensory dominance. A total of 49 volatile compounds were identified by gas chromatography, and each defect was characterized by a specific profile. The e-nose data were analyzed using principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA). The different defects were clearly separated from each other and from the control treatment, independently of PPD intensity. Moreover, the e-nose differentiated control olives from table olives with combined sensory defects despite the dilution effect resulting from the combination. These results demonstrate that e-nose can be used as an olfactory sensor for the organoleptic classification of table olives and can successfully support the tasting panel.

Published
2021
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