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2. 261P Liquid biopsy–based biomarkers for the characterization of hormone receptor-positive (HR+) HER2-Low metastatic breast cancer (mBC)

Author

Bortot, L., primary, Basile, D., additional, Palmero, L., additional, Dri, A., additional, Cucciniello, L., additional, Buriolla, S., additional, Pastò, B., additional, Mazzeo, R., additional, Bonotto, M., additional, Bolzonello, S., additional, Franzoni, A., additional, Allegri, L., additional, Belletti, B., additional, Damante, G., additional, Gerratana, L., additional, Minisini, A.M.M., additional, and Puglisi, F., additional

Published
2022
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3. 416P Prognostic impact of liquid biopsy (LB) biomarkers at relapse on second-line (2L) treatment (Tx) after progression to endocrine therapy (ET) in metastatic breast cancer (mBC): Ancillary analysis of the MAGNETIC.1 study

Author

Dri, A., Foffano, L., Molteni, E., Franzoni, A., Lay, L., Cucciniello, L., Da Ros, L., Buriolla, S., Bolzonello, S., Noto, C., Russo, S., Spazzapan, S., Nascimbeni, E., Pastò, B., Bonotto, M., Minisini, A.M.M., Damante, G., Belletti, B., Gerratana, L., and Puglisi, F.

Published
2024
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6. 294P Cell-free DNA (cfDNA) workflow for the risk definition of dose-limiting and recurrent neutropenia in patients treated with first-line endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) for metastatic breast cancer (MBC)

Author

Palmero, L., primary, Mazzeo, R., additional, Buriolla, S., additional, Bortot, L., additional, Franzoni, A., additional, Michelotti, A., additional, Turra, G., additional, Zilli, M., additional, Stefani, E.C., additional, Allegri, L., additional, Di Nardo, P., additional, Roncato, R., additional, Bonotto, M., additional, Cecchin, E., additional, Belletti, B., additional, Toffoli, G., additional, Baldassarre, G., additional, Damante, G., additional, Gerratana, L., additional, and Puglisi, F., additional

Published
2021
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7. 293P Exploring the interplay between tumor burden and liquid biopsy longitudinal evaluation in hormone receptor-positive, HER2-negative metastatic breast cancer (MBC)

Author

Mazzeo, R., primary, Bortot, L., additional, Michelotti, A., additional, Buriolla, S., additional, Palmero, L., additional, Franzoni, A., additional, Bertoli, E., additional, Targato, G., additional, Allegri, L., additional, Da Ros, L., additional, Alberti, M., additional, Di Nardo, P., additional, Bonotto, M., additional, Sodde, S., additional, Belletti, B., additional, Spazzapan, S., additional, Baldassarre, G., additional, Damante, G., additional, Gerratana, L., additional, and Puglisi, F., additional

Published
2021
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10. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

Author

Barnes D.R., Silvestri V., Leslie G., McGuffog L., Dennis J., Yang X., Adlard J., Agnarsson B.A., Ahmed M., Aittomaki K., Andrulis I.L., Arason A., Arnold N., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Belotti M., Benitez J., Berthet P., Boonen S.E., Borg A., Bozsik A., Brady A., Brennan P., Brewer C., Brunet J., Bucalo A., Buys S.S., Caldes T., Caligo M.A., Campbell I., Cassingham H., Lotte Christensen L., Cini G., Claes K.B.M., Cook J., Coppa A., Cortesi L., Damante G., Darder E., Davidson R., de la Hoya M., De Leeneer K., de Putter R., Del Valle J., Diez O., Chun Ding Y., Domchek S.M., Donaldson A., Eason J., Eeles R., Engel C., Gareth Evans D., Feliubadalo L., Fostira F., Frone M., Frost D., Gallagher D., Gehrig A., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gregory H., Gross E., Hahnen E., Hamann U., Hansen T.V.O., Hanson H., Hentschel J., Horvath J., Izatt L., Izquierdo A., James P.A., Janavicius R., Birk Jensen U., Johannsson O.T., John E.M., Kramer G., Kroeldrup L., Kruse T.A., Lautrup C., Lazaro C., Lesueur F., Lopez-Fernandez A., Mai P.L., Manoukian S., Matrai Z., Matricardi L., Maxwell K.N., Mebirouk N., Meindl A., Montagna M., Monteiro A.N., Morrison P.J., Muranen T.A., Murray A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nguyen-Dumont T., Niederacher D., Olah E., Olopade O.I., Palli D., Parsons M.T., Sokilde Pedersen I., Peissel B., Perez-Segura P., Peterlongo P., Petersen A.H., Pinto P., Porteous M.E., Pottinger C., Angel Pujana M., Radice P., Ramser J., Rantala J., Robson M., Rogers M.T., Ronlund K., Rump A., Maria Sanchez de Abajo A., Shah P.D., Sharif S., Side L.E., Singer C.F., Stadler Z., Steele L., Stoppa-Lyonnet D., Sutter C., Yen Tan Y., Teixeira M.R., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Tommasi S., Toss A., Trainer A.H., Tripathi V., Valentini V., van Asperen C.J., Venturelli M., Viel A., Vijai J., Walker L., Wang-Gohrke S., Wappenschmidt B., Whaite A., Zanna I., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Chenevix-Trench G., Antoniou A.C., Ottini L., Barnes D.R., Silvestri V., Leslie G., McGuffog L., Dennis J., Yang X., Adlard J., Agnarsson B.A., Ahmed M., Aittomaki K., Andrulis I.L., Arason A., Arnold N., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Belotti M., Benitez J., Berthet P., Boonen S.E., Borg A., Bozsik A., Brady A., Brennan P., Brewer C., Brunet J., Bucalo A., Buys S.S., Caldes T., Caligo M.A., Campbell I., Cassingham H., Lotte Christensen L., Cini G., Claes K.B.M., Cook J., Coppa A., Cortesi L., Damante G., Darder E., Davidson R., de la Hoya M., De Leeneer K., de Putter R., Del Valle J., Diez O., Chun Ding Y., Domchek S.M., Donaldson A., Eason J., Eeles R., Engel C., Gareth Evans D., Feliubadalo L., Fostira F., Frone M., Frost D., Gallagher D., Gehrig A., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gregory H., Gross E., Hahnen E., Hamann U., Hansen T.V.O., Hanson H., Hentschel J., Horvath J., Izatt L., Izquierdo A., James P.A., Janavicius R., Birk Jensen U., Johannsson O.T., John E.M., Kramer G., Kroeldrup L., Kruse T.A., Lautrup C., Lazaro C., Lesueur F., Lopez-Fernandez A., Mai P.L., Manoukian S., Matrai Z., Matricardi L., Maxwell K.N., Mebirouk N., Meindl A., Montagna M., Monteiro A.N., Morrison P.J., Muranen T.A., Murray A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nguyen-Dumont T., Niederacher D., Olah E., Olopade O.I., Palli D., Parsons M.T., Sokilde Pedersen I., Peissel B., Perez-Segura P., Peterlongo P., Petersen A.H., Pinto P., Porteous M.E., Pottinger C., Angel Pujana M., Radice P., Ramser J., Rantala J., Robson M., Rogers M.T., Ronlund K., Rump A., Maria Sanchez de Abajo A., Shah P.D., Sharif S., Side L.E., Singer C.F., Stadler Z., Steele L., Stoppa-Lyonnet D., Sutter C., Yen Tan Y., Teixeira M.R., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Tommasi S., Toss A., Trainer A.H., Tripathi V., Valentini V., van Asperen C.J., Venturelli M., Viel A., Vijai J., Walker L., Wang-Gohrke S., Wappenschmidt B., Whaite A., Zanna I., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Chenevix-Trench G., Antoniou A.C., and Ottini L.

Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHOD(S): 483 BRCA1 and 1,318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were three versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen-receptor (ER) negative (PRSER-) or ER-positive (PRSER+) breast cancer risk. RESULT(S): PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07-1.83) for BRCA1 and 1.33 (95% CI=1.16-1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for both BRCA1 (OR=1.73, 95% CI=1.28-2.33) and BRCA2 (OR=1.60, 95% CI=1.34-1.91) carriers. The estimated breast cancer ORs were larger after adjusting for female relative breast cancer family history. By age 85years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSION(S): Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and to inform clinical management.Copyright © The Author(s) 2021. Published by Oxford University Press.

Published
2021

11. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, DR, Silvestri, V, Leslie, G, McGuffog, L, Dennis, J, Yang, X, Adlard, J, Agnarsson, BA, Ahmed, M, Aittomaki, K, Andrulis, IL, Arason, A, Arnold, N, Auber, B, Azzollini, J, Balmana, J, Barkardottir, RB, Barrowdale, D, Barwell, J, Belotti, M, Benitez, J, Berthet, P, Boonen, SE, Borg, A, Bozsik, A, Brady, AF, Brennan, P, Brewer, C, Brunet, J, Bucalo, A, Buys, SS, Caldes, T, Caligo, MA, Campbell, I, Cassingham, H, Christensen, LL, Cini, G, Claes, KBM, Cook, J, Coppa, A, Cortesi, L, Damante, G, Darder, E, Davidson, R, de la Hoya, M, De Leeneer, K, de Putter, R, Del Valle, J, Diez, O, Ding, YC, Domchek, SM, Donaldson, A, Eason, J, Eeles, R, Engel, C, Evans, DG, Feliubadalo, L, Fostira, F, Frone, M, Frost, D, Gallagher, D, Gehrig, A, Giraud, S, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gregory, H, Gross, E, Hahnen, E, Hamann, U, Hansen, TVO, Hanson, H, Hentschel, J, Horvath, J, Izatt, L, Izquierdo, A, James, PA, Janavicius, R, Jensen, UB, Johannsson, OT, John, EM, Kramer, G, Kroeldrup, L, Kruse, TA, Lautrup, C, Lazaro, C, Lesueur, F, Lopez-Fernandez, A, Mai, PL, Manoukian, S, Matrai, Z, Matricardi, L, Maxwell, KN, Mebirouk, N, Meindl, A, Montagna, M, Monteiro, AN, Morrison, PJ, Muranen, TA, Murray, A, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Tu, N-D, Niederacher, D, Olah, E, Olopade, O, Palli, D, Parsons, MT, Pedersen, IS, Peissel, B, Perez-Segura, P, Peterlongo, P, Petersen, AH, Pinto, P, Porteous, ME, Pottinger, C, Pujana, MA, Radice, P, Ramser, J, Rantala, J, Robson, M, Rogers, MT, Ronlund, K, Rump, A, Sanchez de Abajo, AM, Shah, PD, Sharif, S, Side, LE, Singer, CF, Stadler, Z, Steele, L, Stoppa-Lyonnet, D, Sutter, C, Tan, YY, Teixeira, MR, Teule, A, Thull, DL, Tischkowitz, M, Toland, AE, Tommasi, S, Toss, A, Trainer, AH, Tripathi, V, Valentini, V, van Asperen, CJ, Venturelli, M, Viel, A, Vijai, J, Walker, L, Wang-Gohrke, S, Wappenschmidt, B, Whaite, A, Zanna, I, Offit, K, Thomassen, M, Couch, FJ, Schmutzler, RK, Simard, J, Easton, DF, Chenevix-Trench, G, Antoniou, AC, Ottini, L, Barnes, DR, Silvestri, V, Leslie, G, McGuffog, L, Dennis, J, Yang, X, Adlard, J, Agnarsson, BA, Ahmed, M, Aittomaki, K, Andrulis, IL, Arason, A, Arnold, N, Auber, B, Azzollini, J, Balmana, J, Barkardottir, RB, Barrowdale, D, Barwell, J, Belotti, M, Benitez, J, Berthet, P, Boonen, SE, Borg, A, Bozsik, A, Brady, AF, Brennan, P, Brewer, C, Brunet, J, Bucalo, A, Buys, SS, Caldes, T, Caligo, MA, Campbell, I, Cassingham, H, Christensen, LL, Cini, G, Claes, KBM, Cook, J, Coppa, A, Cortesi, L, Damante, G, Darder, E, Davidson, R, de la Hoya, M, De Leeneer, K, de Putter, R, Del Valle, J, Diez, O, Ding, YC, Domchek, SM, Donaldson, A, Eason, J, Eeles, R, Engel, C, Evans, DG, Feliubadalo, L, Fostira, F, Frone, M, Frost, D, Gallagher, D, Gehrig, A, Giraud, S, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gregory, H, Gross, E, Hahnen, E, Hamann, U, Hansen, TVO, Hanson, H, Hentschel, J, Horvath, J, Izatt, L, Izquierdo, A, James, PA, Janavicius, R, Jensen, UB, Johannsson, OT, John, EM, Kramer, G, Kroeldrup, L, Kruse, TA, Lautrup, C, Lazaro, C, Lesueur, F, Lopez-Fernandez, A, Mai, PL, Manoukian, S, Matrai, Z, Matricardi, L, Maxwell, KN, Mebirouk, N, Meindl, A, Montagna, M, Monteiro, AN, Morrison, PJ, Muranen, TA, Murray, A, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Tu, N-D, Niederacher, D, Olah, E, Olopade, O, Palli, D, Parsons, MT, Pedersen, IS, Peissel, B, Perez-Segura, P, Peterlongo, P, Petersen, AH, Pinto, P, Porteous, ME, Pottinger, C, Pujana, MA, Radice, P, Ramser, J, Rantala, J, Robson, M, Rogers, MT, Ronlund, K, Rump, A, Sanchez de Abajo, AM, Shah, PD, Sharif, S, Side, LE, Singer, CF, Stadler, Z, Steele, L, Stoppa-Lyonnet, D, Sutter, C, Tan, YY, Teixeira, MR, Teule, A, Thull, DL, Tischkowitz, M, Toland, AE, Tommasi, S, Toss, A, Trainer, AH, Tripathi, V, Valentini, V, van Asperen, CJ, Venturelli, M, Viel, A, Vijai, J, Walker, L, Wang-Gohrke, S, Wappenschmidt, B, Whaite, A, Zanna, I, Offit, K, Thomassen, M, Couch, FJ, Schmutzler, RK, Simard, J, Easton, DF, Chenevix-Trench, G, Antoniou, AC, and Ottini, L

Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2021

12. 415P Patterns of time-to-progression intervals across clinical and liquid biopsy (LB) features in hormone receptor-positive (HR+) HER2-negative (HER2-) metastatic breast cancer (MBC) patients (pts) treated with first-line endocrine therapy (ET)

Author

Cucciniello, L., Noto, C., Bolzonello, S., Molteni, E., Da Ros, L., Pastò, B., Franzoni, A., Spazzapan, S., Russo, S., Foffano, L., Buriolla, S., Targato, G., Allegri, L., Dri, A., Della Rossa, S., Bonotto, M., Damante, G., Belletti, B., Gerratana, L., and Puglisi, F.

Published
2023
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14. Expression of periostin in human breast cancer

Author

Puglisi, F., Puppin, C., Pegolo, E., Andreetta, C., Pascoletti, G., D'Aurizio, F., Pandolfi, M., Fasola, G., Piga, A., Damante, G., and Di Loreto, C.

Subjects
Proteins -- Research, Proteins -- Physiological aspects, Breast cancer -- Research, Breast cancer -- Genetic aspects, Gene expression -- Research, Neovascularization -- Research, Neovascularization -- Physiological aspects, Health
Published
2008

15. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, V.L., Busch, E.L., Friebel, T.M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Alducci, E., Andrulis, I.L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., Azzollini, J., Balmana, J., Barkardottir, R.B., Barnes, D.R., Barroso, A., Barrowdale, D., Belotti, M., Benitez, J., Bertelsen, B., Blok, M.J., Bodrogi, I., Bonadona, V., Bonanni, B., Bondavalli, D., Boonen, S.E., Borde, J., Borg, A., Bradbury, A.R., Brady, A., Brewer, C., Brunet, J., Buecher, B., Buys, S.S., Cabezas-Camarero, S., Caldes, T., Caliebe, A., Caligo, M.A., Calvello, M., Campbell, I.G., Carnevali, I., Carrasco, E., Chan, T.L., Chu, A.T.W., Chung, W.K., Claes, K.B.M., Cook, J., Cortesi, L., Couch, F.J., Daly, M.B., Damante, G., Darder, E., Davidson, R., Hoya, M. de la, Puppa, L.D., Dennis, J., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Donaldson, A., Dworniczak, B., Easton, D.F., Eccles, D.M., Eeles, R.A., Ehrencrona, H., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Faust, U., Feliubadalo, L., Foretova, L., Fostira, F., Fountzilas, G., Frost, D., Garcia-Barberan, V., Garre, P., Gauthier-Villars, M., Geczi, L., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gutierrez-Barrera, A.M., Hahnen, E., Hamann, U., Mensenkamp, A.R., Nielsen, H., Rebbeck, T.R., Patel, V.L., Busch, E.L., Friebel, T.M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Alducci, E., Andrulis, I.L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., Azzollini, J., Balmana, J., Barkardottir, R.B., Barnes, D.R., Barroso, A., Barrowdale, D., Belotti, M., Benitez, J., Bertelsen, B., Blok, M.J., Bodrogi, I., Bonadona, V., Bonanni, B., Bondavalli, D., Boonen, S.E., Borde, J., Borg, A., Bradbury, A.R., Brady, A., Brewer, C., Brunet, J., Buecher, B., Buys, S.S., Cabezas-Camarero, S., Caldes, T., Caliebe, A., Caligo, M.A., Calvello, M., Campbell, I.G., Carnevali, I., Carrasco, E., Chan, T.L., Chu, A.T.W., Chung, W.K., Claes, K.B.M., Cook, J., Cortesi, L., Couch, F.J., Daly, M.B., Damante, G., Darder, E., Davidson, R., Hoya, M. de la, Puppa, L.D., Dennis, J., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Donaldson, A., Dworniczak, B., Easton, D.F., Eccles, D.M., Eeles, R.A., Ehrencrona, H., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Faust, U., Feliubadalo, L., Foretova, L., Fostira, F., Fountzilas, G., Frost, D., Garcia-Barberan, V., Garre, P., Gauthier-Villars, M., Geczi, L., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gutierrez-Barrera, A.M., Hahnen, E., Hamann, U., Mensenkamp, A.R., Nielsen, H., and Rebbeck, T.R.

Abstract

Contains fulltext : 218251.pdf (Publisher’s version ) (Closed access), Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

Published
2020

16. Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness.

Author

Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., Scarpitta R., Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., and Scarpitta R.

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR 1/4 1.78; 95% confidence interval (CI), 1.25-2.52; P 1/4 0.001], as well as elevated risk of Gleason 8 prostate cancer (HR 1/4 3.11; 95% CI, 1.63-5.95; P 1/4 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR 1/4 2.83; 95% CI, 1.71-4.68; P 1/4 0.00004) and elevated risk of Gleason 8 prostate cancer (HR 1/4 4.95; 95% CI, 2.12-11.54; P 1/4 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer.Copyright © 2020 American Association for Cancer Research.

Published
2020

17. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, VL, Busch, EL, Friebel, TM, Cronin, A, Leslie, G, McGuffog, L, Adlard, J, Agata, S, Agnarsson, BA, Ahmed, M, Aittomaki, K, Alducci, E, Andrulis, IL, Arason, A, Arnold, N, Artioli, G, Arver, B, Auber, B, Azzollini, J, Balmana, J, Barkardottir, RB, Barnes, DR, Barroso, A, Barrowdale, D, Belotti, M, Benitez, J, Bertelsen, B, Blok, MJ, Bodrogi, I, Bonadona, V, Bonanni, B, Bondavalli, D, Boonen, SE, Borde, J, Borg, A, Bradbury, AR, Brady, A, Brewer, C, Brunet, J, Buecher, B, Buys, SS, Cabezas-Camarero, S, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Campbell, IG, Carnevali, I, Carrasco, E, Chan, TL, Chu, ATW, Chung, WK, Claes, KBM, Cook, J, Cortesi, L, Couch, FJ, Daly, MB, Damante, G, Darder, E, Davidson, R, de la Hoya, M, Della Puppa, L, Dennis, J, Diez, O, Ding, YC, Ditsch, N, Domchek, SM, Donaldson, A, Dworniczak, B, Easton, DF, Eccles, DM, Eeles, RA, Ehrencrona, H, Ejlertsen, B, Engel, C, Evans, DG, Faivre, L, Faust, U, Feliubadalo, L, Foretova, L, Fostira, F, Fountzilas, G, Frost, D, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Geczi, L, Gehrig, A, Gerdes, A-M, Gesta, P, Giannini, G, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gutierrez-Barrera, AM, Hahnen, E, Hamann, U, Hauke, J, Herold, N, Hogervorst, FBL, Honisch, E, Hopper, JL, Hulick, PJ, Izatt, L, Jager, A, James, P, Janavicius, R, Jensen, UB, Jensen, TD, Johannsson, OT, John, EM, Joseph, V, Kang, E, Kast, K, Kiiski, J, Kim, S-W, Kim, Z, Ko, K-P, Konstantopoulou, I, Kramer, G, Krogh, L, Kruse, TA, Kwong, A, Larsen, M, Lasset, C, Lautrup, C, Lazaro, C, Lee, J, Lee, JW, Lee, MH, Lemke, J, Lesueur, F, Liljegren, A, Lindblom, A, Llovet, P, Lopez-Fernandez, A, Lopez-Perolio, I, Lorca, V, Loud, JT, Ma, ESK, Mai, PL, Manoukian, S, Mari, V, Martin, L, Matricardi, L, Mebirouk, N, Medici, V, Meijers-Heijboer, HEJ, Meindl, A, Mensenkamp, AR, Miller, C, Gomes, DM, Montagna, M, Mooij, TM, Moserle, L, Mouret-Fourme, E, Mulligan, AM, Nathanson, KL, Navratilova, M, Nevanlinna, H, Niederacher, D, Nielsen, FCC, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, O, Ong, K-R, Osorio, A, Ott, C-E, Palli, D, Park, SK, Parsons, MT, Pedersen, IS, Peissel, B, Peixoto, A, Perez-Segura, P, Peterlongo, P, Petersen, AH, Porteous, ME, Angel Pujana, M, Radice, P, Ramser, J, Rantala, J, Rashid, MU, Rhiem, K, Rizzolo, P, Robson, ME, Rookus, MA, Rossing, CM, Ruddy, KJ, Santos, C, Saule, C, Scarpitta, R, Schmutzler, RK, Schuster, H, Senter, L, Seynaeve, CM, Shah, PD, Sharma, P, Shin, VY, Silvestri, V, Simard, J, Singer, CF, Skytte, A-B, Snape, K, Solano, AR, Soucy, P, Southey, MC, Spurdle, AB, Steele, L, Steinemann, D, Stoppa-Lyonnet, D, Stradella, A, Sunde, L, Sutter, C, Tan, YY, Teixeira, MR, Teo, SH, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tommasi, S, Torres, D, Toss, A, Trainer, AH, Tung, N, van Asperen, CJ, van der Baan, FH, van der Kolk, LE, van der Luijt, RB, van Hest, LP, Varesco, L, Varon-Mateeva, R, Viel, A, Vierstrate, J, Villa, R, von Wachenfeldt, A, Wagner, P, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Wieme, G, Yadav, S, Yannoukakos, D, Yoon, S-Y, Zanzottera, C, Zorn, KK, D'Amico, A, Freedman, ML, Pomerantz, MM, Chenevix-Trench, G, Antoniou, AC, Neuhausen, SL, Ottini, L, Nielsen, HR, Rebbeck, TR, Patel, VL, Busch, EL, Friebel, TM, Cronin, A, Leslie, G, McGuffog, L, Adlard, J, Agata, S, Agnarsson, BA, Ahmed, M, Aittomaki, K, Alducci, E, Andrulis, IL, Arason, A, Arnold, N, Artioli, G, Arver, B, Auber, B, Azzollini, J, Balmana, J, Barkardottir, RB, Barnes, DR, Barroso, A, Barrowdale, D, Belotti, M, Benitez, J, Bertelsen, B, Blok, MJ, Bodrogi, I, Bonadona, V, Bonanni, B, Bondavalli, D, Boonen, SE, Borde, J, Borg, A, Bradbury, AR, Brady, A, Brewer, C, Brunet, J, Buecher, B, Buys, SS, Cabezas-Camarero, S, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Campbell, IG, Carnevali, I, Carrasco, E, Chan, TL, Chu, ATW, Chung, WK, Claes, KBM, Cook, J, Cortesi, L, Couch, FJ, Daly, MB, Damante, G, Darder, E, Davidson, R, de la Hoya, M, Della Puppa, L, Dennis, J, Diez, O, Ding, YC, Ditsch, N, Domchek, SM, Donaldson, A, Dworniczak, B, Easton, DF, Eccles, DM, Eeles, RA, Ehrencrona, H, Ejlertsen, B, Engel, C, Evans, DG, Faivre, L, Faust, U, Feliubadalo, L, Foretova, L, Fostira, F, Fountzilas, G, Frost, D, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Geczi, L, Gehrig, A, Gerdes, A-M, Gesta, P, Giannini, G, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gutierrez-Barrera, AM, Hahnen, E, Hamann, U, Hauke, J, Herold, N, Hogervorst, FBL, Honisch, E, Hopper, JL, Hulick, PJ, Izatt, L, Jager, A, James, P, Janavicius, R, Jensen, UB, Jensen, TD, Johannsson, OT, John, EM, Joseph, V, Kang, E, Kast, K, Kiiski, J, Kim, S-W, Kim, Z, Ko, K-P, Konstantopoulou, I, Kramer, G, Krogh, L, Kruse, TA, Kwong, A, Larsen, M, Lasset, C, Lautrup, C, Lazaro, C, Lee, J, Lee, JW, Lee, MH, Lemke, J, Lesueur, F, Liljegren, A, Lindblom, A, Llovet, P, Lopez-Fernandez, A, Lopez-Perolio, I, Lorca, V, Loud, JT, Ma, ESK, Mai, PL, Manoukian, S, Mari, V, Martin, L, Matricardi, L, Mebirouk, N, Medici, V, Meijers-Heijboer, HEJ, Meindl, A, Mensenkamp, AR, Miller, C, Gomes, DM, Montagna, M, Mooij, TM, Moserle, L, Mouret-Fourme, E, Mulligan, AM, Nathanson, KL, Navratilova, M, Nevanlinna, H, Niederacher, D, Nielsen, FCC, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, O, Ong, K-R, Osorio, A, Ott, C-E, Palli, D, Park, SK, Parsons, MT, Pedersen, IS, Peissel, B, Peixoto, A, Perez-Segura, P, Peterlongo, P, Petersen, AH, Porteous, ME, Angel Pujana, M, Radice, P, Ramser, J, Rantala, J, Rashid, MU, Rhiem, K, Rizzolo, P, Robson, ME, Rookus, MA, Rossing, CM, Ruddy, KJ, Santos, C, Saule, C, Scarpitta, R, Schmutzler, RK, Schuster, H, Senter, L, Seynaeve, CM, Shah, PD, Sharma, P, Shin, VY, Silvestri, V, Simard, J, Singer, CF, Skytte, A-B, Snape, K, Solano, AR, Soucy, P, Southey, MC, Spurdle, AB, Steele, L, Steinemann, D, Stoppa-Lyonnet, D, Stradella, A, Sunde, L, Sutter, C, Tan, YY, Teixeira, MR, Teo, SH, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tommasi, S, Torres, D, Toss, A, Trainer, AH, Tung, N, van Asperen, CJ, van der Baan, FH, van der Kolk, LE, van der Luijt, RB, van Hest, LP, Varesco, L, Varon-Mateeva, R, Viel, A, Vierstrate, J, Villa, R, von Wachenfeldt, A, Wagner, P, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Wieme, G, Yadav, S, Yannoukakos, D, Yoon, S-Y, Zanzottera, C, Zorn, KK, D'Amico, A, Freedman, ML, Pomerantz, MM, Chenevix-Trench, G, Antoniou, AC, Neuhausen, SL, Ottini, L, Nielsen, HR, and Rebbeck, TR

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

Published
2020

18. Performance of a dual-component molecular assay in cytologically indeterminate thyroid nodules

Author

Sponziello, M, Brunelli, C, Verrienti, A, Grani, G, Pecce, V, Abballe, L, Ramundo, V, Damante, G, Russo, D, Lombardi, Cp, Durante, C, Rossi, Ed, Straccia, P, Fadda, G, Filetti, S., Brunelli C, Lombardi CP (ORCID:0000-0001-8910-6693), Straccia P, Fadda G (ORCID:0000-0003-2013-7293), Sponziello, M, Brunelli, C, Verrienti, A, Grani, G, Pecce, V, Abballe, L, Ramundo, V, Damante, G, Russo, D, Lombardi, Cp, Durante, C, Rossi, Ed, Straccia, P, Fadda, G, Filetti, S., Brunelli C, Lombardi CP (ORCID:0000-0001-8910-6693), Straccia P, and Fadda G (ORCID:0000-0003-2013-7293)

Abstract

Performance of a dual-component molecular assay in cytologically indeterminate thyroid nodules

Published
2020

33. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

Author

Lecarpentier, J., Silvestri, V., Kuchenbaecker, K.B., Barrowdale, D., Dennis, J., McGuffog, L., Soucy, P., Leslie, G., Rizzolo, P., Navazio, A.S., Valentini, V., Zelli, V., Lee, A., Olama, A.A. al, Tyrer, J.P., Southey, M., John, E.M., Conner, T.A., Goldgar, D.E., Buys, S.S., Janavicius, R., Steele, L., Ding, Y.C., Neuhausen, S.L., Hansen, T.V.O., Osorio, A., Weitzel, J.N., Toss, A., Medici, V., Cortesi, L., Zanna, I., Palli, D., Radice, P., Manoukian, S., Peissel, B., Azzollini, J., Viel, A., Cini, G., Damante, G., Tommasi, S., Peterlongo, P., Fostira, F., Hamann, U., Evans, D.G., Henderson, A., Brewer, C., Eccles, D., Cook, J., Ong, K.R., Walker, L., Side, L.E., Porteous, M.E., Davidson, R., Hodgson, S., Frost, D., Adlard, J., Izatt, L., Eeles, R., Ellis, S., Tischkowitz, M., Godwin, A.K., Meindl, A., Gehrig, A., Dworniczak, B., Sutter, C., Engel, C., Niederacher, D., Steinemann, D., Hahnen, E., Hauke, J., Rhiem, K., Kast, K., Arnold, N., Ditsch, N., Wang-Gohrke, S., Wappenschmidt, B., Wand, D., Lasset, C., Stoppa-Lyonnet, D., Belotti, M., Damiola, F., Barjhoux, L., Mazoyer, S., Heetvelde, M. van, Poppe, B., Leeneer, K. de, Claes, K.B.M., Hoya, M. de la, Garcia-Barberan, V., Caldes, T., Perez Segura, P., Kiiski, J.I., Aittomaki, K., Khan, S., Nevanlinna, H., Asperen, C.J. van, Vaszko, T., Kasler, M., Olah, E., Balmana, J., Gutierrez-Enriquez, S., Diez, O., Teule, A., Izquierdo, A., Darder, E., Brunet, J., Valle, J. del, Feliubadalo, L., Pujana, M.A., Lazaro, C., Arason, A., Agnarsson, B.A., Johannsson, O.T., Barkardottir, R.B., Alducci, E., Tognazzo, S., Montagna, M., Teixeira, M.R., Pinto, P., Spurdle, A.B., Holland, H., Lee, J.W., Lee, M.H., Lee, J., Kim, S.W., Kang, E., Kim, Z., Sharma, P., Rebbeck, T.R., Vijai, J., Robson, M., Lincoln, A., Musinsky, J., Gaddam, P., Tan, Y.Y., Berger, A., Singer, C.F., Loud, J.T., Greene, M.H., Mulligan, A.M., Glendon, G., Andrulis, I.L., Toland, A.E., Senter, L., Bojesen, A., Nielsen, H.R., Skytte, A.B., Sunde, L., Jensen, U.B., Pedersen, I.S., Krogh, L., Kruse, T.A., Caligo, M.A., Yoon, S.Y., Teo, S.H., Wachenfeldt, A. von, Huo, D., Nielsen, S.M., Olopade, O.I., Nathanson, K.L., Domchek, S.M., Lorenchick, C., Jankowitz, R.C., Campbell, I., James, P., Mitchell, G., Orr, N., Park, S.K., Thomassen, M., Offit, K., Couch, F.J., Simard, J., Easton, D.F., Chenevix-Trench, G., Schmutzler, R.K., Antoniou, A.C., Ottini, L., EMBRACE, GEMO Study Collaborators, HEBON, KConFab Investigators, Dennis, Joe [0000-0003-4591-1214], Leslie, Goska [0000-0001-5756-6222], Lee, Andrew [0000-0003-0677-0252], Amin Al Olama, Ali [0000-0002-7178-3431], Tyrer, Jonathan [0000-0003-3724-4757], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], and Apollo - University of Cambridge Repository

Subjects
Adult, Aged, 80 and over, Male, Heterozygote, Multifactorial Inheritance, Genes, BRCA2, Age Factors, Genes, BRCA1, Prostatic Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, Breast Neoplasms, Male, Case-Control Studies, Mutation, Humans, Genetic Predisposition to Disease, Genetic Testing, skin and connective tissue diseases, Aged, Genome-Wide Association Study
Abstract

$\textbf{Purpose}$ $\textit{BRCA1/2}$ mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of $\textit{BRCA1/2}$ mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of $\textit{BRCA1/2}$ mutations and implications for cancer risk prediction. $\textbf{Materials and Methods}$ We genotyped 1,802 male carriers of $\textit{BRCA1/2}$ mutations from the Consortium of Investigators of Modifiers of $\textit{BRCA1/2}$ by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of $\textit{BRCA1/2}$ mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. $\textbf{Results}$ In male carriers of $\textit{BRCA1/2}$ mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; $P$ = 8.6 × 10$^{-6}$)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; $P$ = 3.2 × 10$^{-9}$)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of $\textit{BRCA1}$ mutations and from 19% to 61% for carriers of $\textit{BRCA2}$ mutations, respectively. $\textbf{Conclusion}$ PRSs may provide informative cancer risk stratification for male carriers of $\textit{BRCA1/2}$ mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

Published
2017

35. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

Author

Lecarpentier, J, Silvestri, V, Kuchenbaecker, KB, Barrowdale, D, Dennis, J, McGuffog, L, Soucy, P, Leslie, G, Rizzolo, P, Navazio, AS, Valentini, V, Zelli, V, Lee, A, Al Olama, AA, Tyrer, JP, Southey, M, John, EM, Conner, TA, Goldgar, DE, Buys, SS, Janavicius, R, Steele, L, Ding, YC, Neuhausen, SL, Hansen, TVO, Osorio, A, Weitzel, JN, Toss, A, Medici, V, Cortesi, L, Zanna, I, Palli, D, Radice, P, Manoukian, S, Peissel, B, Azzollini, J, Viel, A, Cini, G, Damante, G, Tommasi, S, Peterlongo, P, Fostira, F, Hamann, U, Evans, DG, Henderson, A, Brewer, C, Eccles, D, Cook, J, Ong, K-R, Walker, L, Side, LE, Porteous, ME, Davidson, R, Hodgson, S, Frost, D, Adlard, J, Izatt, L, Eeles, R, Ellis, S, Tischkowitz, M, Godwin, AK, Meindl, A, Gehrig, A, Dworniczak, B, Sutter, C, Engel, C, Niederacher, D, Steinemann, D, Hahnen, E, Hauke, J, Rhiem, K, Kast, K, Arnold, N, Ditsch, N, Wang-Gohrke, S, Wappenschmidt, B, Wand, D, Lasset, C, Stoppa-Lyonnet, D, Belotti, M, Damiola, F, Barjhoux, L, Mazoyer, S, Van Heetvelde, M, Poppe, B, De Leeneer, K, Claes, KBM, de la Hoya, M, Garcia-Barberan, V, Caldes, T, Perez Segura, P, Kiiski, JI, Aittomaeki, K, Khan, S, Nevanlinna, H, van Asperen, CJ, Vaszko, T, Kasler, M, Olah, E, Balmana, J, Gutierrez-Enriquez, S, Diez, O, Teule, A, Izquierdo, A, Darder, E, Brunet, J, Del Valle, J, Feliubadalo, L, Pujana, MA, Lazaro, C, Arason, A, Agnarsson, BA, Johannsson, OT, Barkardottir, RB, Alducci, E, Tognazzo, S, Montagna, M, Teixeira, MR, Pinto, P, Spurdle, AB, Holland, H, Lee, JW, Lee, MH, Lee, J, Kim, S-W, Kang, E, Kim, Z, Sharma, P, Rebbeck, TR, Vijai, J, Robson, M, Lincoln, A, Musinsky, J, Gaddam, P, Tan, YY, Berger, A, Singer, CF, Loud, JT, Greene, MH, Mulligan, AM, Glendon, G, Andrulis, IL, Toland, AE, Senter, L, Bojesen, A, Nielsen, HR, Skytte, A-B, Sunde, L, Jensen, UB, Pedersen, IS, Krogh, L, Kruse, TA, Caligo, MA, Yoon, S-Y, Teo, S-H, von Wachenfeldt, A, Huo, D, Nielsen, SM, Olopade, OI, Nathanson, KL, Domchek, SM, Lorenchick, C, Jankowitz, RC, Campbell, I, James, P, Mitchell, G, Orr, N, Park, SK, Thomassen, M, Offit, K, Couch, FJ, Simard, J, Easton, DF, Chenevix-Trench, G, Schmutzler, RK, Antoniou, AC, Ottini, L, Lecarpentier, J, Silvestri, V, Kuchenbaecker, KB, Barrowdale, D, Dennis, J, McGuffog, L, Soucy, P, Leslie, G, Rizzolo, P, Navazio, AS, Valentini, V, Zelli, V, Lee, A, Al Olama, AA, Tyrer, JP, Southey, M, John, EM, Conner, TA, Goldgar, DE, Buys, SS, Janavicius, R, Steele, L, Ding, YC, Neuhausen, SL, Hansen, TVO, Osorio, A, Weitzel, JN, Toss, A, Medici, V, Cortesi, L, Zanna, I, Palli, D, Radice, P, Manoukian, S, Peissel, B, Azzollini, J, Viel, A, Cini, G, Damante, G, Tommasi, S, Peterlongo, P, Fostira, F, Hamann, U, Evans, DG, Henderson, A, Brewer, C, Eccles, D, Cook, J, Ong, K-R, Walker, L, Side, LE, Porteous, ME, Davidson, R, Hodgson, S, Frost, D, Adlard, J, Izatt, L, Eeles, R, Ellis, S, Tischkowitz, M, Godwin, AK, Meindl, A, Gehrig, A, Dworniczak, B, Sutter, C, Engel, C, Niederacher, D, Steinemann, D, Hahnen, E, Hauke, J, Rhiem, K, Kast, K, Arnold, N, Ditsch, N, Wang-Gohrke, S, Wappenschmidt, B, Wand, D, Lasset, C, Stoppa-Lyonnet, D, Belotti, M, Damiola, F, Barjhoux, L, Mazoyer, S, Van Heetvelde, M, Poppe, B, De Leeneer, K, Claes, KBM, de la Hoya, M, Garcia-Barberan, V, Caldes, T, Perez Segura, P, Kiiski, JI, Aittomaeki, K, Khan, S, Nevanlinna, H, van Asperen, CJ, Vaszko, T, Kasler, M, Olah, E, Balmana, J, Gutierrez-Enriquez, S, Diez, O, Teule, A, Izquierdo, A, Darder, E, Brunet, J, Del Valle, J, Feliubadalo, L, Pujana, MA, Lazaro, C, Arason, A, Agnarsson, BA, Johannsson, OT, Barkardottir, RB, Alducci, E, Tognazzo, S, Montagna, M, Teixeira, MR, Pinto, P, Spurdle, AB, Holland, H, Lee, JW, Lee, MH, Lee, J, Kim, S-W, Kang, E, Kim, Z, Sharma, P, Rebbeck, TR, Vijai, J, Robson, M, Lincoln, A, Musinsky, J, Gaddam, P, Tan, YY, Berger, A, Singer, CF, Loud, JT, Greene, MH, Mulligan, AM, Glendon, G, Andrulis, IL, Toland, AE, Senter, L, Bojesen, A, Nielsen, HR, Skytte, A-B, Sunde, L, Jensen, UB, Pedersen, IS, Krogh, L, Kruse, TA, Caligo, MA, Yoon, S-Y, Teo, S-H, von Wachenfeldt, A, Huo, D, Nielsen, SM, Olopade, OI, Nathanson, KL, Domchek, SM, Lorenchick, C, Jankowitz, RC, Campbell, I, James, P, Mitchell, G, Orr, N, Park, SK, Thomassen, M, Offit, K, Couch, FJ, Simard, J, Easton, DF, Chenevix-Trench, G, Schmutzler, RK, Antoniou, AC, and Ottini, L

Abstract

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10-6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10-9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

Published
2017

37. Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the North-East of Italy and improved mutation analysis strategy

Author

Cini, G, Mezzavilla, M, Della Puppa, L, Cupelli, E, Fornasin, A, D'Elia, AV, Dolcetti, R, Damante, G, Bertok, S, Miolo, G, Maestro, R, de Paoli, P, Amoroso, A, Viel, A, Cini, G, Mezzavilla, M, Della Puppa, L, Cupelli, E, Fornasin, A, D'Elia, AV, Dolcetti, R, Damante, G, Bertok, S, Miolo, G, Maestro, R, de Paoli, P, Amoroso, A, and Viel, A

Abstract

BACKGROUND: About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions. In some populations, especially if relatively isolated, a few number of recurrent mutations is reported, sometimes caused by founder effect. METHODS: BRCA1 and BRCA2 screening for mutations was carried out on 1114 breast and/or ovarian cancer patients complying with the eligibility criteria for BRCA testing. Haplotype analysis was performed on the probands carrying recurrent mutations and their relatives, using two sets of microsatellite markers covering the BRCA1 (D17S588, D17S806, D17S902, D17S1325, D17S855, D17S1328, D17S800, and D17S250) and BRCA2 (D13S220, D13S267, D13S171, D13S1701, D13S1698, D13S260, D13S290, D13S1246) loci. The DMLE + 2.2 software was used to estimate the age of BRCA1 c.676delT and BRCA2 c.7806-2A > G. A multiplex PCR and two different primer extension assays were optimized and used for genotyping the recurrent mutations of the two genes. RESULTS: In the time frame of almost 20 years of genetic testing, we have found that five BRCA1 and three BRCA2 mutations are recurrent in a substantial subset of carriers from North-East Italy and neighboring Istria, where they represent more than 50 % of all mutations. Microsatellite analyses identified a common haplotype of different length for each mutation. Age estimation of BRCA1 c.676delT and BRCA2 c.7806-2A > G mutations revealed that they arose in the Friuli Venezia Giulia area about 86 and 94 generations ago, respectively. Suggestion of an association between BRCA2 c.7806-2A > G and risk of breast cancer in males has emerged. Finally, we developed a simple and efficient pre-screening test, performing an in-house primer extension SNaPshot® assay for the rapid identification of the eight recurrent mutations. CONCLUSIONS: Proofs of common ancestry has

Published
2016

38. Genetic analysis of 'PAX6-negative' individuals with aniridia or Gillespie Syndrome

Author

Ansari, M, Rainger, J, Hanson, IM, Williamson, KA, Sharkey, F, Harewood, L, Sandilands, A, Clayton-Smith, J, Dollfus, H, Bitoun, P, Meire, F, Fantes, J, Franco, B, Lorenz, B, Taylor, DS, Stewart, F, Willoughby, CE, McEntagart, M, Khaw, PT, Clericuzio, C, Van Maldergem, L, Williams, D, Newbury-Ecob, R, Traboulsi, EI, Silva, ED, Madlom, MM, Goudie, DR, Fleck, BW, Wieczorek, D, Kohlhase, J, McTrusty, AD, Gardiner, C, Yale, C, Moore, AT, Russell-Eggitt, I, Islam, L, Lees, M, Beales, PL, Tuft, SJ, Solano, JB, Splitt, M, Hertz, JM, Prescott, TE, Shears, DJ, Nischal, KK, Doco-Fenzy, M, Prieur, F, Temple, IK, Lachlan, KL, Damante, G, Morrison, DA, Van Heyningen, V, Fitzpatrick, DR, Ansari, M, Rainger, J, Hanson, IM, Williamson, KA, Sharkey, F, Harewood, L, Sandilands, A, Clayton-Smith, J, Dollfus, H, Bitoun, P, Meire, F, Fantes, J, Franco, B, Lorenz, B, Taylor, DS, Stewart, F, Willoughby, CE, McEntagart, M, Khaw, PT, Clericuzio, C, Van Maldergem, L, Williams, D, Newbury-Ecob, R, Traboulsi, EI, Silva, ED, Madlom, MM, Goudie, DR, Fleck, BW, Wieczorek, D, Kohlhase, J, McTrusty, AD, Gardiner, C, Yale, C, Moore, AT, Russell-Eggitt, I, Islam, L, Lees, M, Beales, PL, Tuft, SJ, Solano, JB, Splitt, M, Hertz, JM, Prescott, TE, Shears, DJ, Nischal, KK, Doco-Fenzy, M, Prieur, F, Temple, IK, Lachlan, KL, Damante, G, Morrison, DA, Van Heyningen, V, and Fitzpatrick, DR

Abstract

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3′ (telomeric) to PAX6 and one within a gene desert 5′ (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p. Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.

Published
2016

41. Expression and localization of the homeodomain-containing protein HEX in human thyroid tumors

Author

DELIA A., TELL G., RUSSO D., ARTURI F., PUGLISI F., GATTEI V., MACK D. L., CATALDI P., FILETTI S., DI LORETO C. AND DAMANTE G. EXPRESSION AND LOCALIZATION OF THE HOMEODOMAIN CONTAINING PROTEIN HEX IN HUMAN THYROID T.U.M.O.R.S. J. C.L.I.N. E.N.D.O.C.R.I.N.O.L. M.E.T.A.B., MANFIOLETTI, GUIDALBERTO, Delia, A., Tell, G., Russo, D., Arturi, F., Puglisi, F., Manfioletti, Guidalberto, Gattei, V., Mack, D. L., Cataldi, P., Filetti, S., and DI LORETO, C. AND DAMANTE G. EXPRESSION AND LOCALIZATION OF THE HOMEODOMAIN CONTAINING PROTEIN HEX IN HUMAN THYROID T. U. M. O. R. S. J. C. L. I. N. E. N. D. O. C. R. I. N. O. L. M. E. T. A. B.

Published
2002

42. ApeI/Ref-I expression and cellular localization in human thyroid carcinoma cell lines

Author

Russo, D., Arturi, F., Bullota, S., Pellizzari, L., Filetti, S., Manzini, G., Damante, G., Gianluca Tell, Russo, D, Arturi, F, Bulotta, S, Pellizzari, L, Filetti, S, Manzini, Giorgio, Damante, G, and Tell, G.

Subjects
Adenoma, Cell Nucleus, Cytoplasm, DNA Repair, Blotting, Western, Carbon-Oxygen Lyases, Carcinoma, ApeI/Ref-I, Thyroid tumoral cells, apei/ref-i, nuclear/cytoplasmic ratio, redox potential, thyroid tumoral cells, Diabetes and Metabolism, Nuclear/cytoplasmic ratio, Redox potential, Endocrinology, Diabetes and Metabolism, Endocrinology, DNA-(Apurinic or Apyrimidinic Site) Lyase, Tumor Cells, Cultured, Humans, Thyroid Neoplasms
Abstract

For its DNA repair, transcription factor regulation and anti-apoptotic activity, the apurinic/apirimidinic ApeI/Ref-I endonuclease is thought to play a relevant role in human tumorigenesis. In human thyroid tumors, we demonstrated an altered nuclear/cytoplasmic ratio in all the carcinomas examined but not in follicular adenomas. In this study, Ref-I expression and cellular localization were analyzed in a series of human thyroid carcinoma cell lines. We found a reduced nuclear/cytoplasmic ratio in BCPAP, TPC I and ARO cells and not in WRO cells. Such a pattern of expression corresponds to that observed in thyroid tumoral tissues except for the WRO cells which behave as the follicular adenomas rather than carcinomas. Thus, these cell lines represent an excellent in vitro model to analyze the molecular mechanisms involved in Ref-I regulation and activity and clarify its role in thyroid tumorigenesis.

Published
2001

43. Levels of histone acetylation in thyroid tumors

Author

Puppin, C, Passon, N, Lavarone, E, Di Loreto, C, Frasca, Francesco, Vella, V, Vigneri, R, Damante, G., and Vella, Veronica

Subjects
endocrine system, endocrine system diseases, Biophysics, Biochemistry, Thyroid carcinoma, Histones, Cell Line, Tumor, medicine, Tumor Cells, Cultured, Animals, Humans, Neoplastic transformation, Epigenetics, Thyroid Neoplasms, Molecular Biology, biology, Thyroid, Acetylation, Cell Biology, Rats, Histone, medicine.anatomical_structure, Tumor progression, biology.protein, Cancer research, Protein Processing, Post-Translational, Hormone
Abstract

Histone acetylation is a major mechanism to regulate gene transcription. This post-translational modification is modified in cancer cells. In various tumor types the levels of acetylation at several histone residues are associated to clinical aggressiveness. By using immunohistochemistry we show that acetylated levels of lysines at positions 9–14 of H3 histone (H3K9–K14ac) are significantly higher in follicular adenomas (FA), papillary thyroid carcinomas (PTC), follicular thyroid carcinomas (FTC) and undifferentiated carcinomas (UC) than in normal tissues (NT). Similar data have been obtained when acetylated levels of lysine 18 of H3 histone (H3K18ac) were evaluated. In this case, however, no difference was observed between NT and UC. When acetylated levels of lysine 12 of H4 histone (H4K12ac) were evaluated, only FA showed significantly higher levels in comparison with NT. These data indicate that modification histone acetylation is an early event along thyroid tumor progression and that H3K18 acetylation is switched off in the transition between differentiated and undifferentiated thyroid tumors. By using rat thyroid cell lines that are stably transfected with doxycyclin-inducible oncogenes, we show that the oncoproteins RET–PTC, RAS and BRAF increase levels of H3K9–K14ac and H3K18ac. In the non-tumorigenic rat thyroid cell line FRTL-5, TSH increases levels of H3K18ac. However, this hormone decreases levels of H3K9–K14ac and H4K12ac. In conclusion, our data indicate that neoplastic transformation and hormonal stimulation can modify levels of histone acetylation in thyroid cells.

Published
2011

44. Cross-linking of HLA class II antigens modulates the release of tumor necrosis factor-alpha by the EBV-B lymphoblastoid cell line JY

Author

Altomonte M, Carlo Pucillo, Damante G, and Maio M

Subjects
B-Lymphocytes, Herpesvirus 4, Human, Superantigens, Tumor Necrosis Factor-alpha, Immunology, Histocompatibility Antigens Class II, NF-kappa B, Antibodies, Monoclonal, Cell Transformation, Viral, Humans, Immunology and Allergy, Cell Division, Cell Aggregation, Cell Line, Transformed
Abstract

In addition to their functional role as peptide-binding proteins HLA class II Ag can also act as signal-transducing molecules. The present study showed that cross-linking of HLA class II Ag by the anti-HLA-DR mAb L243 or by the anti-HLA-DR,-DP mAb IVA12 significantly (p < 0.05) increased the release of TNF-alpha by the EBV-B lymphoblastoid cell line JY. In contrast, the anti-HLA-DR mAb 2.06 or the superantigens staphylococcal exotoxin toxic shock syndrome toxin-1 and staphylococcal enterotoxin B that bind to HLA-DR,-DQ Ag did not affect the release of TNF-alpha by JY cells. The accumulation of TNF-alpha in the culture medium of JY cells peaked at 24 h, decreased thereafter, and was found to be dependent on the dose of mAb L243 or mAb IVA12 used to cross-link HLA class II Ag. mAb L243 or staphylococcal exotoxin toxic shock syndrome toxin-1 enhanced the spontaneous homotypic aggregation of JY cells and mediated a dose-dependent inhibition of JY cell proliferation. These phenomena were not mediated by TNF-alpha released in response to cross-linking of HLA class II Ag; polyclonal anti-TNF-alpha neutralizing antibody did not affect JY cell aggregation and the inhibition of JY cell proliferation mediated by mAb L243. In contrast, TNF-alpha secreted by JY cells enhanced a nuclear factor-kB-like activity through the binding to the 75-kDa TNF-alpha receptor. These results demonstrate an additional role of HLA class II Ag as signal-transducing molecules regulating the production of bioactive TNF-alpha by EBV-B cells. The release of TNF-alpha after the triggering of HLA class II molecules could be relevant to different aspects of B cell biology and might play a role in the pathogenesis of human diseases in which antibodies cross-reactive to HLA class II Ag have been identified.

Published
1993

46. Thyroid tumors: novel insights from proteomic studies

Author

Damante G, Scaloni A, and Tell G.

Abstract

Several genomics-based techniques have been applied in the last decade to the molecular characterization of cancer, which has led to a variety of applications suitable for improved diagnosis, prognosis and prediction of outcome to treatment. Proteomics-based approaches have also been seen as crucial to the discovery of biomarkers for early diagnosis and prognosis of tumors, as well as for a better understanding of the molecular bases of cancer. Accordingly, proteomic techniques have been used extensively for a better molecular characterization of thyroid tumors. In this field, three main directions have been preceded: first, proteomic studies of model systems; second, proteomics of thyroid tumor specimens; and third, serum proteomics. In this review, we describe the most relevant results that have been obtained for tumors derived from thyroid follicular cells using various proteomic approaches.

Published
2009

47. Down-regulation of SM22/transgelin gene expression during H9c2 cells differentiation

Author

Bregant E, Renzone G, Lonigro R, Passon N, Di Loreto C, Pandolfi M, Scaloni A, Tell G, and Damante G.

Abstract

The embryonic rat ventricle H9c2 cells maintain a proliferative state (P condition) in the presence of 10% FCS. However, by reducing serum concentration and in the presence of retinol acetate, proliferation is stopped, myogenic transdifferentiation is inhibited while cardiac differentiation is preserved (D condition). Two-dimensional gel electrophoresis and mass spectrometry analysis was used to define the modifications of the nuclear proteome occurring during the P-to-D transition. Among the proteins observed as modified, a reduced expression of the SM22/transgelin protein was associated with the D state. Also SM22 mRNA levels were reduced during P-to-D transition. Cell transfection experiments indicated that this decrease was partially due to a reduction of the SM22 promoter activity. GATA-4 had a repressive effect on SM22 promoter activity. Thus, since GATA-4 is known as a target of retinoids and may act as a transcriptional repressor, a mechanism to explain the SM22 reduction during the P-to-D transition is tentatively proposed. Immunohistochemical studies on heart cells confirmed the nuclear localization of SM22. Moreover, a differential expression of this protein in different districts of the human heart embryo was detected. Therefore, these data suggest that SM22 expression is regulated during heart development.

Published
2009

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