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3. Targeting DDX3 with a small molecule inhibitor for lung cancer therapy

Author

Bol, Guus M, Vesuna, Farhad, Xie, Min, Zeng, Jing, Aziz, Khaled, Gandhi, Nishant, Levine, Anne, Irving, Ashley, Korz, Dorian, Tantravedi, Saritha, Heerma van Voss, Marise R, Gabrielson, Kathleen, Bordt, Evan A, Polster, Brian M, Cope, Leslie, van der Groep, Petra, Kondaskar, Atul, Rudek, Michelle A, Hosmane, Ramachandra S, van der Wall, Elsken, van Diest, Paul J, Tran, Phuoc T, and Raman, Venu

Published
2015
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28. Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer

Author

Severson, T.M. (Tesa), Kim, Y. (Yongsoo), Joosten, S.E.P. (Stacey E. P.), Schuurman, K.G. (Karianne), van der Groep, P. (Petra), Moelans, C.B. (Cathy), Hoeve, N.D. (Natalie) ter, Manson, Q.F. (Quirine F.), Martens, J.W.M. (John), Deurzen, C.H.M. (Carolien) van, Barbe, E. (Ellis), Hedenfalk, I. (Ingrid), Bult, P. (Peter), Smit, V.T.H.B.M. (Vincent), Linn, S.C. (Sabine C.), Diest, P.J. (Paul) van, Wessels, L. (Lodewyk), Zwart, W. (Wilbert), Severson, T.M. (Tesa), Kim, Y. (Yongsoo), Joosten, S.E.P. (Stacey E. P.), Schuurman, K.G. (Karianne), van der Groep, P. (Petra), Moelans, C.B. (Cathy), Hoeve, N.D. (Natalie) ter, Manson, Q.F. (Quirine F.), Martens, J.W.M. (John), Deurzen, C.H.M. (Carolien) van, Barbe, E. (Ellis), Hedenfalk, I. (Ingrid), Bult, P. (Peter), Smit, V.T.H.B.M. (Vincent), Linn, S.C. (Sabine C.), Diest, P.J. (Paul) van, Wessels, L. (Lodewyk), and Zwart, W. (Wilbert)

Abstract

Male breast cancer (MBC) is rare and largely hormonally driven. Here, the authors examine the action of steroid hormone receptors in male and female breast cancers and find gender selective hormone receptor action that associates with the survival of MBC patients.

Published
2018
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29. P003 Implementation of High Throughput Parallel Sequencing in a Diagnostic Setting: Multiplexed Amplicon Sequencing of the Breast Cancer Genes BRCA1 and 2

Author

Zogopoulos G, Tomi Pastinen, Sivanandan K, Vaca F, Kinoshita T, Johannes B, Leguis E, Jansen-van der Weide M, Learn L, Godlewski D, Ed Saunders, Montserrat Rué, Vaisman A, de Bock G, Ángel Segura, Sabbaghian N, Mohammad Amin Kerachian, Pelletier S, Metcalfe K, Lilge L, Stockle E, Cheng S, Burger C, Woike A, Michelle Guy, Ragone A, Y. J. Bignon, Bronkhorst Y, Patricia N. Tonin, Lima M, Mieke Kriege, Karsan A, Zweemer R, Prady C, Beattie M, Panchal S, Kathleen Claes, van Zon P, Diane Provencher, Ummels A, Kang I, Shumak R, Arcusa Â, Yosr Hamdi, Alonso Mc, Dolman L, Houssami N, Olivier Delattre, Yannick Bidet, Claude Houdayer, Mercedes Durán, Ganschow P, Isabel Chirivella, Domingo S, Rebsamen M, Giustina Simone, Orland Diez, Chapman J, An tSaoir C, Jeanna McCuaig, Blayney J, Bosdet I, Treacy R, Esther Darder, Ando J, Luc Dehaspe, García-Casado Z, Duffy J, Harkin D, Z Kote-Jarai, Kasamatsu T, Ulf Kristoffersson, Membrez, Priston M, Noreau-Heisz D, Trivedi A, Begoña Graña, Ghadirian P, Ashuryk O, Consol López, Wenzel L, Vogel R, Joseph G, Poll A, Kennedy R, Patton S, Pérez C, Mónica Cornet, Panighetti A, Cassart P, Burke K, Mes-Masson A, Llacuachaqui M, Marc Tischkowitz, Wong N, Arcand S, Kotsopoulos J, Meschino W, Hall A, Marles S, Docking R, Haroun I, Marie Plante, Rachel Laframboise, Daniel Sinnett, Luce J, Sekiguchi I, Edenir Inêz Palmero, de Winter J, Christopher J. Lord, Hamel N, Pruski-Clark J, Lee D, Rusnak A, Carson N, Marta Santamariña, Knoppers B, Oakhill K, Bruce R. Rosen, Pierre O. Chappuis, Bruce Poppe, Stanislaw C, Catts Z, Brood M, van der Wall E, Yip C, Christine Walsh, Hoodfar E, Pressman A, Andrulis I, Alicia Barroso, D. Leongamornlert, Gillian Mitchell, Akira Hirasawa, Shen Z, Sameer Parpia, Horgan M, van Echtelt J, Chun K, Lubinski J, Rebecca Sutphen, Terespolsky D, Richard D, McDyer F, Floquet A, Lambo R, Bathurst L, Brown G, Kidd M, Nicolas Sevenet, Mourits M, Vencken P, Tatiana Popova, Garcia N, Armel S, van Amstel H, Valentini A, Ellen Warner, Hofland N, Hanna D, Kim J, Osann K, Enmore M, Loranger K, Sulivan I, J. Oliveira, Meijers H, Jansen R, Edmundo Carvalho Mauad, Kirkpatrick R, Danilo V Viana, Ian G. Campbell, Mil S, E J Sawyer, J. Balmaña, Samra Turajlic, Graham G, Alonso C, Inanc Birol, Sinclair F, van Tuil M, Pascual Bolufer, Micheli R, Andrew R. Green, Junyent N, Whittaker J, Monnerat C, Rhéaume J, Livingston D, Chan S, L. Ramadan, Lee R, Katarzyna Durda, De Leeneer K, Grados C, Côté C, Kyle B. Matchett, Robert Winqvist, Bonner D, Brunella Pilato, Mohd Taib N, Judy Garber, Kleiderman E, Murakami S, Sharifi N, Kimberley Hill, Desbiens C, Robert Royer, Jasperson K, Hsieh S, De Summa S, Dominique Stoppa-Lyonnet, de Lima J, Stuart McIntosh, Shakeri M, Wendy Kohlmann, Albert-Green A, de Hullu J, Pasick R, Avard D, Pathania S, van der Groep P, Laura Fachal, Bruno Zeitouni, Susan M. Domchek, Davey S, Richard Marais, Powell C, Hans J. J. P. Gille, Greenberg R, Kamata H, Cina, Gaarenstroom K, Lakhal Chaieb M, Kavanagh L, Gaelle Benais-Pont, Sun P, Jansen L, Matthew Parker, Barjhoux L, Russ H, Simon J. Furney, Willems A, Robb L, David E. Goldgar, Young S, Natalia Campacci, Mark G. Thomas, Doug Easton, Klugman S, Barrault M, Calvo N, Adriana C. Flora, Littell R, Narod S, Fragoso, N. Bosch, Finch A, Paul M. Wilkerson, Teo S, Tomasz Huzarski, Manuel Salto-Tellez, Moseley M, Davis S, Olga M. Sinilnikova, Iturbe A, Joan Brunet, Tierney M, Tsai E, Navarro de Souza A, Leclerc M, Lorenzo Manti, Gutiérrez-Enríquez S, Milewski B, Simon S. McDade, Kaplan C, Buckley N, Eva Esteban-Cardeñosa, Richter S, Shimizu C, Li J, Elena Castro, Iwanka Kozarewa, Harley I, Atocha Romero, Carlos E. Andrade, Carole Verny-Pierre, Barouk E, Vian D, Montserrat Baiget, Chan J, Sandra Bonache, Andrew Y Shuen, van der Merwe N, Kaklewski K, Mohar A, Tamura C, Heale E, Rooyadeh M, van Asperen C, Gemma Llort, Alan Mackay, Denroche R, Seelaus C, Zbuk K, McCluggage W, van der Luijt R, Maaike P.G. Vreeswijk, Edelweiss M, Crossan G, Arseneau J, Ambus I, Verheul H, Rodrigo Augusto Depieri Michelli, Juul T. Wijnen, Gross-Lester J, Britta Weigelt, Pedro Pérez-Segura, Richard A. Moore, Cornelissen C, Larouche G, McAlpine J, Daniel Nava Rodrigues, Trim L, Furnival J, Elser C, Muszyńka M, Adriana Lasa, Tuya Pal, Greuter. M, Ng K, Dorval M, Bresee C, Reimnitz G, Gaëtan MacGrogan, Perry Maxwell, Barnadas A, Hwang E, Powell B, Knapke S, Griskevicius. L, Alvarez R, Mester J, Anne-Bine Skytte, Eladio Velasco, Vidal S, Australie K, Leunen K, Ben-Yishay M, Van Houdt J, Phuah S, Amy E Taylor, Pinto R, Fonseca T, Champine M, Gammon A, Hollema H, Menko F, Feng B, David Olmos, Chong G, Tomasz Byrski, Patrick J. Morrison, Gregoire J, André Lopes Carvalho, Don B. Plewes, Rabeneck L, Carrol J, Alan Ashworth, Terlinge A, A Jakubowska, Odette Mariani, Setareh Moghadasi, Reitsma W, Rothenmund H, Herrera L, Anna Tenés, Angel Izquierdo, Asunción Torres, Stawicka M, Goh C, Hirst M, Drummond J, Osorio A, Ostrovsky R, Jeffrey N. Weitzel, Gareth W. Irwin, Fehniger J, Sugano K, Spriggs E, Dęniak T, Volenik A, Thorne H, Piccinin C, Amie Blanco, Jinno H, Robert A. Holt, Stephen B. Fox, Julia J. Gorski, Gilpin C, Herschorn S, Vega A, E. Page, Hamet P, McKenna D, Fabrice Bonnet, Yoshida T, Kienan I. Savage, Petzel S, Elizabeth Bancroft, Schneider S, Warwick L, Stewart S, William D. Foulkes, Colizza K, Bell K, Demsky R, Malgorzata Tymrakiewicz, Caldés T, Fons G, Bowen D, Côté S, Clouston D, Kitagawa Y, Gordon Glendon, Jenny Lester, Kinney A, Nelson E, Silke Hollants, Macrae L, Cajal T, Andrew J. Mungall, Ferrell B, Creighton B, Bressler L, Uy P, Makishima K, Haffaf Z, Ramūnas Janavičius, Einstein G, Zakalik D, Chiarelli A, Cantu D, Croce S, Kalloger S, Lin F, Ian O. Ellis, Benedito Mauro Rossi, R A Wilkinson, Mulligan J, Murphy J, Vadaparampil S, Smith E, Slangen B, Loiselle C, Iqbal J, Palma L, Cooper K, Jorge S. Reis-Filho, Chen. L, Quinten Waisfisz, Haneda E, Banks P, Vermeulen K, Visser B, Montalbán G, McCabe N, Honeyford J, Naseri S, Ng J, Ali A, Sandrine Viala, Mensa I, Kamarainen O, Guerra C, Mazzola E, David A. Schwartz, Marjanka K. Schmidt, Simon R, Fergus J. Couch, Margreet G. E. M. Ausems, Anne Vincent-Salomon, Olinski R, Zewald R, Moreno R, Semple J, McPherson J, Lamers E, Kharbanda A, Kessler L, Biemans D, Au A, Bordeleau L, Jean Feunteun, Mar Infante, Mullan P, Rudaitis, Molenda A, Rachael Natrajan, Pawar, Boman B, Kok T, Andrew A. Brown, Geller M, Monfared N, Bart J, Murata P, Crawford N, Butterfield Y, Bargalló J, Katherine L. Tucker, Cook-Wiens G, Rhodes A, Elodie Manié, Rubio E, Oram L, Shandiz F, Hayden R, Crawford B, Parmigiani G, Harkin P, Müller C, Grant M, Maryou B. Lambros, Thong M, Grzegorz Sukiennicki, Wouts J, Haddock P, Ramon y Cajal T, Kenneth C. Anderson, Michel Longy, Batiste W, Carroll J, Matte C, Hojyo T, Zhao Y, Caroline Seynaeve, Wai P, Simard J, Hurley K, Bolton D, Karlan B, Javier Benítez, Miriam Masas, Tołczko-Grabarek A, de Dueñas E, Geneviève Michils, Moncoutier, Nancy Uhrhammer, MacDonald D, Keyserlingk J, Osher D, Gilks C, Christopher T. Elliott, Scharf L, Gabram-Mendola S, Grondin K, Dohany L, van Diest P, Joris Vermeesch, Jan C. Oosterwijk, M’Baïlara K, DePuit M, Jacek Gronwald, Stefania Tommasi, de la Hoya M, Bouchard K, Black L, Lui M, Soucy P, Rosalind A. Eeles, Gert Matthijs, Graham T, Andrea Eisen, Bacha O, Alvaro N.A. Monteiro, Yoon S, Caron T, Smith D, Marc-Henri Stern, Hampson E, Kurz R, Gaasbeek W, Mundt E, Angela Velasco, Quinn J, Jocelyne Chiquette, Marquez T, Adam B. Murphy, Bakker J, Neus Gadea, Anita Grigoriadis, Aoki D, Dean S, Looi L, Paradiso A, Agostina Stradella, K. Govindasami, Lovell N, Eva Tomiak, Siesling S, Belanger M, Feilotter H, Knight J, Emmanuel Barillot, Huang M, Raquel Andrés, Kang P, Somerman C, Gackowski D, Rimel B, Nakamura S, McClellan K, Barrros E, Henriette Roed Nielsen, Rui Manuel Reis, Greening S, Ayme A, Carmen Guillen, de Vries E, and Katarzyna Jaworska

Subjects
Oncology, Education and Communication, medicine.medical_specialty, endocrine system diseases, medicine.diagnostic_test, business.industry, Psycho-Oncology, medicine.disease, Meeting Abstracts, Transcriptome, Basic Research, Clinical Management, Germline mutation, Breast cancer, Applied Research, Internal medicine, Mutation (genetic algorithm), medicine, Genetic Counselling, Human genome, skin and connective tissue diseases, business, Ovarian cancer, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract

Background: Germline mutation screening of BRCA1 and BRCA2 genes is performed in suspected familial breast cancer cases, but a causative mutation is found in only 30% of patients. The development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would therefore increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1—or BRCA2—mutated breast cancers. Materials and Methods: Array-cgh (comparative genomic hybridization) and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the basis of at least 3 affected first-degree relatives or at least 2 affected first-degree relatives with breast cancer at an average age of 45 years. Array-cgh analyses were performed on a 4407 BAC-array (CIT-V8) manufactured by IntegraGen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Results: Using supervised clustering analyses we identified two transcriptomic signatures: one for BRCA1-mutated breast cancers consisting of 600 probe sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined cgh-array signatures, based on the presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers. Conclusions: This study identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. We also identified specific genomic rearrangements in these breast cancers, which could be screened for in a diagnostic setting using fluorescence in situ hybridization, thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis.

Published
2009
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31. Recruitment of the Mammalian Histone-modifying EMSY Complex to Target Genes Is Regulated by ZNF131

Author

Varier, R. A., Carrillo de Santa Pau, E., van der Groep, P., Lindeboom, R.G.H., Matarese, F., Mensinga, A., Smits, A.H., Edupuganti, V.S.R.R., Baltissen, M.P., Jansen, P. W., Ter Hoeve, N., van Weely, D.R., Poser, I., van Diest, P.J., Stunnenberg, H., Vermeulen, M., Varier, R. A., Carrillo de Santa Pau, E., van der Groep, P., Lindeboom, R.G.H., Matarese, F., Mensinga, A., Smits, A.H., Edupuganti, V.S.R.R., Baltissen, M.P., Jansen, P. W., Ter Hoeve, N., van Weely, D.R., Poser, I., van Diest, P.J., Stunnenberg, H., and Vermeulen, M.

Abstract

Contains fulltext : 161825.pdf (publisher's version ) (Open Access)

Published
2016

32. Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

Author

Bol, G.M., Raman, V., van der Groep, P., Vermeulen, J.F., Patel, A.H., van der Wall, E., and van Diest, P.J.

Abstract

Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.\ud \ud Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.\ud \ud Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.

Published
2013

35. Immunophenotyping of hereditary breast cancer

Author

van der Groep, P., van der Wall, E., Offerhaus, G.J.A., and University Utrecht

Subjects
endocrine system diseases, skin and connective tissue diseases
Abstract

Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may be missed, and small families and sometimes insufficient medical records may cause uninformative family history. This thesis aimed to investigate the immunoprofile of hereditary breast cancers caused by germline mutations in the BRCA1 or BRCA2 genes in order to identify patients and families eligible for mutation screening. In addition, such studies on hereditary precursors could help to better understand hereditary breast carcinogenesis and identify new therapeutic targets. We started with evaluating a panel of clinicopathological variables to classify breast cancers as hereditary or sporadic using a multivariate approach. Most of the investigated markers were expressed in line with earlier data. However, we were the first to describe the high expression of EGFR in BRCA1 and BRCA2 related breast cancers. In addition, the observed high cyclin A expression is another useful proliferation marker in BRCA1 related breast cancers, and has been herewith established for the first time. Although our data were based on only five cases of BRCA2-related breast cancers, the cyclin D1 expression in these tumours was remarkably high. As such, most invasive breast carcinomas can be classified as sporadic or BRCA1 related with a high degree of certainty using a decision tree based on age, Ki67 and EGFR. Furthermore, we are the first to report that in BRCA1 and BRCA2 mutation carriers the immunoprofile of ductal carcinoma in situ (DCIS), a premalignant lesion, parallels the accompanying invasive cancer lesion, underlining that DCIS is probably a direct precursor lesion in these patients. In addition, crucial carcinogenetic events leading to these phenotypes apparently occur at an early stage in hereditary predisposed patients, most likely even before the stage of DCIS. We describe the novel finding of loss of expression of FANCD2, a Fanconi anaemia gene previously implicated in breast cancer in mice, in hereditary and sporadic invasive breast cancer, indicating that somatic inactivating (epi)genetic events in FANCD2 may occur in both sporadic and hereditary breast carcinogenesis. Our results do however not indicate that somatic (epi)genetic changes in FANCD2 are a frequent secondary carcinogenetic event in BRCA1 germline mutated patients. The expression of HIF-1?, the key regulator of the hypoxia response, in hereditary breast cancer is for the first time reported in comparison with sporadic breast cancer. 90% of BRCA1 germline mutation related breast cancers showed overexpression of HIF-1?, a percentage significantly higher than in sporadic controls. The overexpression of HIF-1? in BRCA1 related breast cancers is a frequent event and is likely hypoxia regulated, suggesting that the HIF-1? pathway plays a role in the BRCA-1 carcinogenesis and progression. All these findings will lead to improved discrimination of the BRCA1 and BRCA2 related breast cancer. Furthermore, the new biomarkers may serve as therapeutic targets for BRCA1 and BRCA2 related breast cancers.

Published
2009

36. Comprehensive Proteomic Profiling–derived Immunohistochemistry-based Prediction Models for BRCA1and BRCA2Germline Mutation-related Breast Carcinomas

Author

Vos, Shoko, Elias, Sjoerd G., van der Groep, Petra, Smolders, Yvonne H., van Gils, Carla H., and van Diest, Paul J.

Abstract

Supplemental Digital Content is available in the text.Heredity, mostly due to BRCAgermline mutations, is involved in 5% to 10% of all breast cancer cases. Potential BRCAgermline mutation carriers may be missed following the current eligibility criteria for BRCAgenetic testing. The purpose of this study was to, therefore, develop an immunohistochemistry-based model to predict likelihood of underlying BRCA1and BRCA2germline mutations in unselected female breast cancer patients. The study group consisted of 100 BRCA1-related, 46 BRCA2-related, and 94 sporadic breast carcinomas. Tumor expression of 44 proteins involved in (BRCA-related) breast carcinogenesis was assessed by immunohistochemistry. A prediction model for BRCA-related versus non–BRCA-related breast cancer was developed using Lasso logistic regression analysis with cross-validation. The model was assessed for its discriminative value and clinical usefulness. The optimal prediction model included 14 predictors (age, cyclinD1, ERα, ERβ, FGFR2, FGFR3, FGFR4, GLUT1, IGFR, Ki67, mitotic activity index, MLH1, p120, and TOP2A), showed excellent discriminative performance (area under the receiving operating characteristic curve=0.943; 95% confidence interval=0.909-0.978), and reasonable calibration. To enhance possible implementation, we developed an alternative model only considering more widely available immunostains. This model included 15 predictors (age, BCL2, CK5/6, CK8/18, cyclinD1, E-cadherin, ERα, HER2, Ki67, mitotic activity index , MLH1, p16, PMS2, PR, and vimentin), and still showed very good discriminative performance (area under the receiving operating characteristic curve=0.853; 95% confidence interval=0.795-0.911). We present a well-applicable and accurate tool to predict which breast cancer patients may have an underlying BRCAgermline mutation, largely consisting of immunohistochemical markers independent of clinical characteristics. This may improve identification of potential BRCAgermline mutation carriers and optimize referral for germline mutation testing.

Published
2018
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38. Regulation of E2F1 by the von Hippel-Lindau tumour suppressor protein predicts survival in renal cell cancer patients

Author

Tissue Repair, Dep Pathobiologie, Mans, D.A., Vermaat, J.S.P., Weijts, B.G.M.W., van Rooijen, E., van Reeuwijk, J., Boldt, K., Daenen, L.G.M., van der Groep, P., Rowland, B., Jans, J.J.M., Roepman, R., Voest, E.E., van Diest, P.J., Verhaar, M.C., de Bruin, A., Giles, R.H., Tissue Repair, Dep Pathobiologie, Mans, D.A., Vermaat, J.S.P., Weijts, B.G.M.W., van Rooijen, E., van Reeuwijk, J., Boldt, K., Daenen, L.G.M., van der Groep, P., Rowland, B., Jans, J.J.M., Roepman, R., Voest, E.E., van Diest, P.J., Verhaar, M.C., de Bruin, A., and Giles, R.H.

Published
2013

40. Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

Author

Cancer, Pathologie, Divisie Beeld & Oncologie, Bol, G.M., Raman, V., van der Groep, P., Vermeulen, J.F., Patel, A.H., van der Wall, E., van Diest, P.J., Cancer, Pathologie, Divisie Beeld & Oncologie, Bol, G.M., Raman, V., van der Groep, P., Vermeulen, J.F., Patel, A.H., van der Wall, E., and van Diest, P.J.

Published
2013

41. HIF-1alpha and NOTCH signaling in ductal and lobular carcinomas of the breast

Author

Ercan, C., Vermeulen, J.F., Hoefnagel, L., Bult, P., van der Groep, P., van der Wall, E., van Diest, P.J., Ercan, C., Vermeulen, J.F., Hoefnagel, L., Bult, P., van der Groep, P., van der Wall, E., and van Diest, P.J.

Abstract

Item does not contain fulltext, BACKGROUND: NOTCH signaling is involved in every step of metazoan development and maintenance of adult tissue homeostasis. It is frequently deregulated by mutations and overexpression in different cancer types including solid tumors such as breast cancer. Another common feature of solid tumors is hypoxia, which occurs due to defective or insufficient vascularization. Hypoxia-inducible factors (HIFs) are key regulators of the homeostatic response to low oxygen levels. HIF-1alpha is overexpressed in many solid tumors, including breast cancer. Hypoxia-induced stabilization of HIF transcription factors has been shown to lead to NOTCH activation in vitro in different contexts and tissues, causing differentiation arrest and induction of proliferation and migration. METHODS: Since the link between HIF-1alpha and NOTCH signalling has hardly been studied, we set out to closely investigate associations between the expression of HIF-1alpha and NOTCH pathway members in primary and metastatic human breast cancer specimens and their prognostic value. RESULTS: Co-expression of NOTCH1 intracellular domain (N1ICD) and HIF-1alpha was associated with a high grade and a high proliferation rate in invasive breast cancer. HIF-1alpha expression was low in classic, but high in pleomorphic lobular cancers, which also frequently showed stromal HIF-1alpha expression. NOTCH1 pathway activation was prognostically unfavorable. CONCLUSION: In breast cancer, NOTCH pathway activation appears to be associated with a poor prognosis, but NOTCH and HIF signaling do not seem to be functionally associated.

Published
2012

43. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

Author

Cancer, Pathologie, Divisie Beeld & Oncologie, Vermeulen, J.F., van Brussel, A.S.A., van der Groep, P., Morsink, F.H.M., Bult, P., van der Wall, E., van Diest, P.J., Cancer, Pathologie, Divisie Beeld & Oncologie, Vermeulen, J.F., van Brussel, A.S.A., van der Groep, P., Morsink, F.H.M., Bult, P., van der Wall, E., and van Diest, P.J.

Published
2012

45. Immunophenotyping of hereditary breast cancer

Author

Cancer, Pathologie, van der Wall, E, Offerhaus, G.J.A., van der Groep, P., Cancer, Pathologie, van der Wall, E, Offerhaus, G.J.A., and van der Groep, P.

Published
2009

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