Center for Molecular Medicine Cologne

Schmutzler, Rita - assoc. RG 20

Investigation of the genetic causes of breast and ovarian cancer

Abstract

Despite the progress in understanding the hereditary basis of familial breast and ovarian cancer, hereditary factors known today, such as changes in the BRCA1/2 genes, can only explain part of all familial cases. Recent data suggest that additional genetic and non-genetic components may contribute multifactorially to the disease and modulate disease risk in the presence of risk gene mutation.

Our goal is to further unravel the diverse architecture of breast and ovarian cancer, identify new risk factors and their interactions, and to make this knowledge available to patients through personalized risk prediction and cancer prevention. To achieve these goals, we work closely with international study groups and coordinate the German Consortium Familial Breast and Ovarian Cancer, which has attracted international attention by identifying new risk genes.

Identification of new risk genes

One focus of our research is the identification of new genes associated with an increased risk of breast and/or ovarian cancer. Since these additional genes are rarely mutated and probably only moderately increase the risk of disease, large collectives of well characterized patients are necessary to detect significant associations with the phenotype. For this purpose we have entered into national and international collaborations to identify additional risk genes. In the PERSPECTIVE study "personalized risk stratification for the prevention and early detection of breast cancer", which we are conducting with Prof. Jacques Simard (Genome Quebec, Canada) and other cooperation partners from the Netherlands and the USA, new candidate genes were identified by exome-wide analyses. For this purpose, exome sequencing was performed in about 1,500 breast cancer (BC) patients. We aim to genetically validate and functionally characterize the newly identified BC candidate risk genes to explore their putative role in BC pathogenesis by using patient-derived LCLs, mouse ES cells, and CRISPR/Cas9-mediated gene silencing. The results of this study will help to further improve the risk calculation for those seeking advice from families in which no mutation has been detected so far.

Polygenic Risk Score (PRS): low-risk variants  for individual risk calculation

Results of our Genome-wide association studies (GWAS) showed that single nucleotide polymorphisms (SNPs) are associated with the risk of developing breast cancer. The risk of individual SNPs is low, so that they are not suitable for risk calculation on an individual basis. However, studies have shown that a combination of several SNPs can have an influence on the risk of developing breast cancer. It is now assumed that the currently known SNPs can explain approximately 18% of the familial breast cancer risk. The multiplicative effect of the variants can be summarized and the so-called PRS can be calculated. At present the calculations of the PRS are based only on models, which are usually limited to BRCA1/2 mutation carriers. A validation of the PRS, especially in familial breast cancer patients, is still pending. Furthermore, it has to be clarified whether the PRS can be applied to mutation carriers of further risk genes and whether a risk stratification of these patients based on the calculation of the PRS is possible. For this project, we are also working closely together with the other German breast cancer centers and international experts (Dr. Karoline Kuchenbäcker, University College London).

Influence of germline mutations on therapy response in patients with breast cancer

The goal of personalized treatment is to administer only those therapies to which patients actually respond. To investigate the effect of germline mutations on therapy response, we are involved in two studies of the German Breast Group (GBG). In the GeparSixto study (NCT01426880), we were able to show by examining the BRCA1/2 germline mutation status in patients with triple-negative breast cancer that BRCA1/2 mutation carriers generally respond well to the neoadjuvant therapy with anthracyclines and taxanes, but do not benefit additionally from the addition of carboplatin. GeparOcto (NCT02125344) is a Phase III clinical trial comparing two different treatment strategies in the treatment of primary breast cancer in high-risk patients. Patients were randomly assigned to one of the two therapeutic arms. In a genetic subproject of the study, we isolate the DNA of the study participants from blood and examine it by means of Next Generation Sequencing (NGS) for pathological germline mutations in the known breast cancer genes BRCA1 and BRCA2 and another 16 potential risk genes suspected to be associated with an increased breast cancer risk. The aim is to gain insight into whether and to what extent the genetic status has an influence on the response to therapy of those affected

Clinical and Medical Relevance

Expanding the current understanding of genetic BC and OC predisposition is a prerequisite for the improvement of individualized risk prediction, cancer prevention by intensified surveillance programs and prophylactic measures and targeted therapy.

The translational impact of our data is supported by direct clinical implementation within the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), as recently shown for new BC/OC risk genes such as BRIP1 and BARD1.

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Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre L, Berthet P, Hooning MJ, van der Kolk LE, Kets CM, Adank MA, John EM, Chung WK, Andrulis IL, Southey M, Daly MB, Buys SS, Osorio A, Engel C, Kast K, Schmutzler RK, Caldes T, Jakubowska A, Simard J, Friedlander ML, McLachlan SA, Machackova E, Foretova L, Tan YY, Singer CF, Olah E, Gerdes AM, Arver B, Olsson H: Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. Jama 2017, 317(23):2402-2416.

Michailidou K, Lindström S, Dennis J, Beesley J, several authors, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schumacher F, Schürmann P, Scott RJ, Scott C, Seal S, Seynaeve C, Shah M, Sharma P, Shen CY, Sheng G, Sherman ME, Shrubsole MJ, Shu XO, Smeets A, Sohn C, Southey MC, Spinelli JJ, Stegmaier C, Stewart-Brown S, Stone J, Stram DO, Surowy H, Swerdlow A, Tamimi R, Taylor JA, Tengström M, Teo SH, Beth Terry M, Tessier DC, Thanasitthichai S, Thöne K, Tollenaar R, Tomlinson I, Tong L, Torres D, Truong T, Tseng CC, Tsugane S, Ulmer HU, Ursin G, Untch M, Vachon C, van Asperen CJ, Van Den Berg D, van den Ouweland AMW, van der Kolk L, van der Luijt RB, Vincent D, Vollenweider J, Waisfisz Q, Wang-Gohrke S, Weinberg CR, Wendt C, Whittemore AS, Wildiers H, Willett W, Winqvist R, Wolk A, Wu AH, Xia L, Yamaji T, Yang XR, Har Yip C, Yoo KY, Yu JC, Zheng W, Zheng Y, Zhu B, Ziogas A, Ziv E, Lakhani SR, Antoniou AC, Droit A, Andrulis IL, Amos CI, Couch FJ, Pharoah PDP, Chang-Claude J, Hall P, Hunter DJ, Milne RL, García-Closas M, Schmidt MK, Chanock SJ, Dunning AM, Edwards SL, Bader GD, Chenevix-Trench G, Simard J, Kraft P, Easton DF: Association analysis identifies 65 new breast cancer risk loci. Nature 2017, 551(7678):92-94.

Neidhardt G, Hauke J, Ramser J, Groß E, Gehrig A, Müller CR, Kahlert AK, Hackmann K, Honisch E, Niederacher D, Heilmann-Heimbach S, Franke A, Lieb W, Thiele H, Altmüller J, Nürnberg P, Klaschik K, Ernst C, Ditsch N, Jessen F, Ramirez A, Wappenschmidt B, Engel C, Rhiem K, Meindl A, Schmutzler RK, Hahnen E: Association Between Loss-of-Function Mutations Within the FANCM Gene and Early-Onset Familial Breast Cancer. JAMA Oncol 2017, 3(9):1245-1248.

Pohl-Rescigno E, Hauke J, Loibl S, Möbus V, Denkert C, Fasching PA, Kayali M, Ernst C, Weber-Lassalle N, Hanusch C, Tesch H, Müller V, Altmüller J, Thiele H, Untch M, Lübbe K, Nürnberg P, Rhiem K, Furlanetto J, Lederer B, Jackisch C, Nekljudova V, Schmutzler RK, Schneeweiss A, Hahnen E: Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol 2020, 6(5):744-748.

Silvestri V, Leslie G, Barnes DR, several authors ,Schmutzler RK, Senter L, Simard J, Singer CF, Solano AR, Southey MC, Steele L, Steinsnyder Z, Stoppa-Lyonnet D, Tan YY, Teixeira MR, Teo SH, Terry MB, Thomassen M, Toland AE, Torres-Esquius S, Tung N, van Asperen CJ, Vega A, Viel A, Vierstraete J, Wappenschmidt B, Weitzel JN, Wieme G, Yoon SY, Zorn KK, McGuffog L, Parsons MT, Hamann U, Greene MH, Kirk JA, Neuhausen SL, Rebbeck TR, Tischkowitz M, Chenevix-Trench G, Antoniou AC, Friedman E, Ottini L: Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). JAMA Oncol 2020, 6(8):1218-1230.

Weber-Lassalle N, Borde J, Weber-Lassalle K, Horváth J, Niederacher D, Arnold N, Kaulfuß S, Ernst C, Paul VG, Honisch E, Klaschik K, Volk AE, Kubisch C, Rapp S, Lichey N, Altmüller J, Lepkes L, Pohl-Rescigno E, Thiele H, Nürnberg P, Larsen M, Richters L, Rhiem K, Wappenschmidt B, Engel C, Meindl A, Schmutzler RK, Hahnen E, Hauke J: Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer. Breast Cancer Res 2019, 21(1):55.

Weber-Lassalle N, Hauke J, Ramser J, Richters L, Groß E, Blümcke B, Gehrig A, Kahlert AK, Müller CR, Hackmann K, Honisch E, Weber-Lassalle K, Niederacher D, Borde J, Thiele H, Ernst C, Altmüller J, Neidhardt G, Nürnberg P, Klaschik K, Schroeder C, Platzer K, Volk AE, Wang-Gohrke S, Just W, Auber B, Kubisch C, Schmidt G, Horvath J, Wappenschmidt B, Engel C, Arnold N, Dworniczak B, Rhiem K, Meindl A, Schmutzler RK, Hahnen E: BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer. Breast Cancer Res 2018, 20(1):7.

Yang X, Leslie G, Doroszuk A, Schneider S, several authors, Schmutzler R, Teo SH, Robson M, Pal T, Couch F, Weitzel JN, Elliott A, Southey M, Winqvist R, Easton DF, Foulkes WD, Antoniou AC, Tischkowitz M: Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J Clin Oncol 2020, 38(7):674-685.

Zhang H, Ahearn TU, Lecarpentier J, serveral authors, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schöttker B, Schürmann P, Senter L, Sharma P, Sherman ME, Shu XO, Singer CF, Smichkoska S, Soucy P, Southey MC, Spinelli JJ, Stone J, Stoppa-Lyonnet D, Swerdlow AJ, Szabo CI, Tamimi RM, Tapper WJ, Taylor JA, Teixeira MR, Terry M, Thomassen M, Thull DL, Tischkowitz M, Toland AE, Tollenaar R, Tomlinson I, Torres D, Troester MA, Truong T, Tung N, Untch M, Vachon CM, van den Ouweland AMW, van der Kolk LE, van Veen EM, vanRensburg EJ, Vega A, Wappenschmidt B, Weinberg CR, Weitzel JN, Wildiers H, Winqvist R, Wolk A, Yang XR, Yannoukakos D, Zheng W, Zorn KK, Milne RL, Kraft P, Simard J, Pharoah PDP, Michailidou K, Antoniou AC, Schmidt MK, Chenevix-Trench G, Easton DF, Chatterjee N, García-Closas M: Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nat Genet 2020, 52(6):572-581.

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                                                                                                                                                                                                                                                                      • Muranen TA, Khan S, Fagerholm R, Aittomaki K, Cunningham JM, Dennis J, Leslie G, McGuffog L, Parsons MT, Simard J, Slager S, Soucy P, Easton DF, Tischkowitz M, Spurdle AB, kConFab I, Schmutzler RK, Wappenschmidt B, Hahnen E, Hooning MJ, Investigators H, Singer CF, Wagner G, Thomassen M, Pedersen IS, Domchek SM, Nathanson KL, Lazaro C, Rossing CM, Andrulis IL, Teixeira MR, James P, Garber J, Weitzel JN, Investigators S-B, Jakubowska A, Yannoukakos D, John EM, Southey MC, Schmidt MK, Antoniou AC, Chenevix-Trench G, Blomqvist C, and Nevanlinna H (2020). Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer. NPJ breast cancer 6, 44.
                                                                                                                                                                                                                                                                      • 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, Collaborators GS, Collaborators E, Cook J, Cortesi L, Couch FJ, Daly MB, Damante G, Darder E, Davidson R, de la Hoya M, Puppa LD, 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 AM, 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, Investigators K, Investigators H, Izatt L, Jager A, James P, Janavicius R, Jensen UB, Jensen TD, Johannsson OT, John EM, Joseph V, Kang E, Kast K, Kiiski JI, Kim SW, Kim Z, Ko KP, 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 OI, Ong KR, Osorio A, Ott CE, Palli D, Park SK, Parsons MT, Pedersen IS, Peissel B, Peixoto A, Perez-Segura P, Peterlongo P, Petersen AH, Porteous ME, Pujana MA, 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 AB, 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, Vierstraete J, Villa R, von Wachenfeldt A, Wagner P, Wang-Gohrke S, Wappenschmidt B, Weitzel JN, Wieme G, Yadav S, Yannoukakos D, Yoon SY, Zanzottera C, Zorn KK, D'Amico AV, Freedman ML, Pomerantz MM, Chenevix-Trench G, Antoniou AC, Neuhausen SL, Ottini L, Nielsen HR, and Rebbeck TR (2020). Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness. Cancer Res 80, 624-38.
                                                                                                                                                                                                                                                                      • Pohl-Rescigno E, Hauke J, Loibl S, Mobus V, Denkert C, Fasching PA, Kayali M, Ernst C, Weber-Lassalle N, Hanusch C, Tesch H, Muller V, Altmuller J, Thiele H, Untch M, Lubbe K, Nurnberg P, Rhiem K, Furlanetto J, Lederer B, Jackisch C, Nekljudova V, Schmutzler RK, Schneeweiss A, and Hahnen E (2020). Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol 10.1001/jamaoncol.2020.0007.
                                                                                                                                                                                                                                                                      • Silvestri V, Leslie G, Barnes DR, Group C, Agnarsson BA, Aittomaki K, Alducci E, Andrulis IL, Barkardottir RB, Barroso A, Barrowdale D, Benitez J, Bonanni B, Borg A, Buys SS, Caldes T, Caligo MA, Capalbo C, Campbell I, Chung WK, Claes KBM, Colonna SV, Cortesi L, Couch FJ, de la Hoya M, Diez O, Ding YC, Domchek S, Easton DF, Ejlertsen B, Engel C, Evans DG, Feliubadalo L, Foretova L, Fostira F, Geczi L, Gerdes AM, Glendon G, Godwin AK, Goldgar DE, Hahnen E, Hogervorst FBL, Hopper JL, Hulick PJ, Isaacs C, Izquierdo A, James PA, Janavicius R, Jensen UB, John EM, Joseph V, Konstantopoulou I, Kurian AW, Kwong A, Landucci E, Lesueur F, Loud JT, Machackova E, Mai PL, Majidzadeh AK, Manoukian S, Montagna M, Moserle L, Mulligan AM, Nathanson KL, Nevanlinna H, Ngeow J, Nikitina-Zake L, Offit K, Olah E, Olopade OI, Osorio A, Papi L, Park SK, Pedersen IS, Perez-Segura P, Petersen AH, Pinto P, Porfirio B, Pujana MA, Radice P, Rantala J, Rashid MU, Rosenzweig B, Rossing M, Santamarina M, Schmutzler RK, Senter L, Simard J, Singer CF, Solano AR, Southey MC, Steele L, Steinsnyder Z, Stoppa-Lyonnet D, Tan YY, Teixeira MR, Teo SH, Terry MB, Thomassen M, Toland AE, Torres-Esquius S, Tung N, van Asperen CJ, Vega A, Viel A, Vierstraete J, Wappenschmidt B, Weitzel JN, Wieme G, Yoon SY, Zorn KK, McGuffog L, Parsons MT, Hamann U, Greene MH, Kirk JA, Neuhausen SL, Rebbeck TR, Tischkowitz M, Chenevix-Trench G, Antoniou AC, Friedman E, and Ottini L (2020). Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). JAMA Oncol 6, 1218-30.
                                                                                                                                                                                                                                                                      • Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, Dunning AM, Redman J, Scarth J, Plaskocinska I, Luccarini C, Shah M, Pooley K, Dorling L, Lee A, Adank MA, Adlard J, Aittomaki K, Andrulis IL, Ang P, Barwell J, Bernstein JL, Bobolis K, Borg A, Blomqvist C, Claes KBM, Concannon P, Cuggia A, Culver JO, Damiola F, de Pauw A, Diez O, Dolinsky JS, Domchek SM, Engel C, Evans DG, Fostira F, Garber J, Golmard L, Goode EL, Gruber SB, Hahnen E, Hake C, Heikkinen T, Hurley JE, Janavicius R, Kleibl Z, Kleiblova P, Konstantopoulou I, Kvist A, Laduca H, Lee ASG, Lesueur F, Maher ER, Mannermaa A, Manoukian S, McFarland R, McKinnon W, Meindl A, Metcalfe K, Mohd Taib NA, Moilanen J, Nathanson KL, Neuhausen S, Ng PS, Nguyen-Dumont T, Nielsen SM, Obermair F, Offit K, Olopade OI, Ottini L, Penkert J, Pylkas K, Radice P, Ramus SJ, Rudaitis V, Side L, Silva-Smith R, Silvestri V, Skytte AB, Slavin T, Soukupova J, Tondini C, Trainer AH, Unzeitig G, Usha L, van Overeem Hansen T, Whitworth J, Wood M, Yip CH, Yoon SY, Yussuf A, Zogopoulos G, Goldgar D, Hopper JL, Chenevix-Trench G, Pharoah P, George SHL, Balmana J, Houdayer C, James P, El-Haffaf Z, Ehrencrona H, Janatova M, Peterlongo P, Nevanlinna H, Schmutzler R, Teo SH, Robson M, Pal T, Couch F, Weitzel JN, Elliott A, Southey M, Winqvist R, Easton DF, Foulkes WD, Antoniou AC, and Tischkowitz M (2020a). Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J Clin Oncol 38, 674-85.
                                                                                                                                                                                                                                                                      • Yang X, Song H, Leslie G, Engel C, Hahnen E, Auber B, Horvath J, Kast K, Niederacher D, Turnbull C, Houlston R, Hanson H, Loveday C, Dolinsky JS, LaDuca H, Ramus SJ, Menon U, Rosenthal AN, Jacobs I, Gayther SA, Dicks E, Nevanlinna H, Aittomaki K, Pelttari LM, Ehrencrona H, Borg A, Kvist A, Rivera B, Hansen TVO, Djursby M, Lee A, Dennis J, Bowtell DD, Traficante N, Diez O, Balmana J, Gruber SB, Chenevix-Trench G, kConFab I, Jensen A, Kjaer SK, Hogdall E, Castera L, Garber J, Janavicius R, Osorio A, Golmard L, Vega A, Couch FJ, Robson M, Gronwald J, Domchek SM, Culver JO, de la Hoya M, Easton DF, Foulkes WD, Tischkowitz M, Meindl A, Schmutzler RK, Pharoah PDP, and Antoniou AC (2020b). Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D. J Natl Cancer Inst 10.1093/jnci/djaa030.
                                                                                                                                                                                                                                                                      Prof. Dr. Rita Schmutzler CMMC Cologne
                                                                                                                                                                                                                                                                      Prof. Dr. Rita Schmutzler

                                                                                                                                                                                                                                                                      Center for Familial Breast- and Ovarian Cancer

                                                                                                                                                                                                                                                                      CMMC - PI - assoc. RG 20

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                                                                                                                                                                                                                                                                      Center for Familial Breast- and Ovarian Cancer

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                                                                                                                                                                                                                                                                      Curriculum Vitae (CV)

                                                                                                                                                                                                                                                                      Publications on PubMed

                                                                                                                                                                                                                                                                      Publications - Rita Schmutzler

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