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1. Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease

Author: Dhanya Ramachandran, Jonathan P. Tyrer, Stefan Kommoss, Anna DeFazio, Marjorie J. Riggan, AOCS Group, Penelope M. Webb, Peter A. Fasching, Diether Lambrechts, María J. García, Cristina Rodríguez-Antona, Marc T. Goodman, Francesmary Modugno, Kirsten B. Moysich, Beth Y. Karlan, Jenny Lester, Susanne K. Kjaer, Allan Jensen, Estrid Høgdall, Ellen L. Goode, William A. Cliby, Amanika Kumar, Chen Wang, Julie M. Cunningham, Stacey J. Winham, Alvaro N. Monteiro, Joellen M. Schildkraut, Daniel W. Cramer, Kathryn L. Terry, Linda Titus, Line Bjorge, Liv Cecilie Vestrheim Thomsen, OPAL Study Group, Tanja Pejovic, Claus K. Høgdall, Iain A. McNeish, Taymaa May, David G. Huntsman, Jacobus Pfisterer, Ulrich Canzler, Tjoung-Won Park-Simon, Willibald Schröder, Antje Belau, Lars Hanker, Philipp Harter, Jalid Sehouli, Rainer Kimmig, Nikolaus de Gregorio, Barbara Schmalfeldt, Klaus Baumann, Felix Hilpert, Alexander Burges, Boris Winterhoff, Peter Schürmann, Lisa-Marie Speith, Peter Hillemanns, Andrew Berchuck, Sharon E. Johnatty, Susan J. Ramus, Georgia Chenevix-Trench, Paul D. P. Pharoah, Thilo Dörk, and Florian Heitz
Subjects: Medicine, Genetics, QH426-470
Abstract: Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10−8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
Published: 2024
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2. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Author: Martin Köbel, Eun‐Young Kang, Ashley Weir, Peter F Rambau, Cheng‐Han Lee, Gregg S Nelson, Prafull Ghatage, Nicola S Meagher, Marjorie J Riggan, Jennifer Alsop, Michael S Anglesio, Matthias W Beckmann, Christiani Bisinotto, Michelle Boisen, Jessica Boros, Alison H Brand, Angela Brooks‐Wilson, Michael E Carney, Penny Coulson, Madeleine Courtney‐Brooks, Kara L Cushing‐Haugen, Cezary Cybulski, Suha Deen, Mona A El‐Bahrawy, Esther Elishaev, Ramona Erber, Sian Fereday, AOCS Group, Anna Fischer, Simon A Gayther, Arantzazu Barquin‐Garcia, Aleksandra Gentry‐Maharaj, C Blake Gilks, Helena Gronwald, Marcel Grube, Paul R Harnett, Holly R Harris, Andreas D Hartkopf, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y Hernandez, Yajue Huang, Anna Jakubowska, Mercedes Jimenez‐Linan, Michael E Jones, Catherine J Kennedy, Tomasz Kluz, Jennifer M Koziak, Jaime Lesnock, Jenny Lester, Jan Lubiński, Teri A Longacre, Maria Lycke, Constantina Mateoiu, Bryan M McCauley, Valerie McGuire, Britta Ney, Alexander Olawaiye, Sandra Orsulic, Ana Osorio, Luis Paz‐Ares, Teresa Ramón y Cajal, Joseph H Rothstein, Matthias Ruebner, Minouk J Schoemaker, Mitul Shah, Raghwa Sharma, Mark E Sherman, Yurii B Shvetsov, Naveena Singh, Helen Steed, Sarah J Storr, Aline Talhouk, Nadia Traficante, Chen Wang, Alice S Whittemore, Martin Widschwendter, Lynne R Wilkens, Stacey J Winham, Javier Benitez, Andrew Berchuck, David D Bowtell, Francisco J Candido dos Reis, Ian Campbell, Linda S Cook, Anna DeFazio, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, María J García, Marc T Goodman, Ellen L Goode, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Linda E Kelemen, Stefan Kommoss, Nhu D Le, Stewart G Martin, Usha Menon, Francesmary Modugno, Paul DP Pharoah, Joellen M Schildkraut, Weiva Sieh, Annette Staebler, Karin Sundfeldt, Anthony J Swerdlow, Susan J Ramus, and James D Brenton
Subjects: ovarian cancer, high‐grade serous carcinoma, endometrioid, clear cell, TP53, p53, Pathology, RB1-214
Abstract: Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Published: 2023
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3. Older age should not be a barrier to testing for somatic variants in homologous recombination DNA repair-related genes in patients with high-grade serous ovarian carcinoma

Author: Omali Pitiyarachchi, Yeh Chen Lee, Hao-Wen Sim, Sivatharsny Srirangan, Cristina Mapagu, Judy Kirk, Paul R. Harnett, Rosemary L. Balleine, David D.L. Bowtell, Goli Samimi, Alison H. Brand, Deborah J. Marsh, Philip Beale, Lyndal Anderson, Natalie Bouantoun, Pamela Provan, Susan J. Ramus, Anna DeFazio, and Michael Friedlander
Subjects: Older patients, Somatic testing, Ovarian cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients. Methods: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed. Cases where somatic variants could be distinguished from germline variants were included, and analysis was restricted to those with a somatic TP53 variant, to ensure cases were HGSC. Results: Of 1210 patients in GENIE, 27% (n = 325) were aged ≥70 years at testing. Patients with somatic-only PVs in BRCA2 were older compared with BRCA1 (median 71 vs 60 years, p = 0.002). Median age for 21 patients with somatic-only PVs in 11 other HR-related genes ranged from 40 to 67 years. In older patients, 7% (n = 22) had somatic BRCA1/2 PVs, and 1% (n = 2) had PVs other HR-related genes; this rate was not significantly different to younger patients (
Published: 2023
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4. Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer

Author: Siddhartha P. Kar, Daniel P.C. Considine, Jonathan P. Tyrer, Jasmine T. Plummer, Stephanie Chen, Felipe S. Dezem, Alvaro N. Barbeira, Padma S. Rajagopal, Will T. Rosenow, Fernando Moreno, Clara Bodelon, Jenny Chang-Claude, Georgia Chenevix-Trench, Anna deFazio, Thilo Dörk, Arif B. Ekici, Ailith Ewing, George Fountzilas, Ellen L. Goode, Mikael Hartman, Florian Heitz, Peter Hillemanns, Estrid Høgdall, Claus K. Høgdall, Tomasz Huzarski, Allan Jensen, Beth Y. Karlan, Elza Khusnutdinova, Lambertus A. Kiemeney, Susanne K. Kjaer, Rüdiger Klapdor, Martin Köbel, Jingmei Li, Clemens Liebrich, Taymaa May, Håkan Olsson, Jennifer B. Permuth, Paolo Peterlongo, Paolo Radice, Susan J. Ramus, Marjorie J. Riggan, Harvey A. Risch, Emmanouil Saloustros, Jacques Simard, Lukasz M. Szafron, Linda Titus, Cheryl L. Thompson, Robert A. Vierkant, Stacey J. Winham, Wei Zheng, Jennifer A. Doherty, Andrew Berchuck, Kate Lawrenson, Hae Kyung Im, Ani W. Manichaikul, Paul D.P. Pharoah, Simon A. Gayther, and Joellen M. Schildkraut
Subjects: breast cancer, ovarian cancer, pleiotropy, GWAS, transcriptome-wide association study, Genetics, QH426-470
Abstract: Summary: Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.
Published: 2021
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5. Publisher Correction: Shared heritability and functional enrichment across six solid cancers

Author: Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R. Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H. M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, and Sara Lindström
Subjects: Science
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
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6. Shared heritability and functional enrichment across six solid cancers

Author: Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, and Sara Lindström
Subjects: Science
Abstract: Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.
Published: 2019
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7. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma

Author: Eun-Young, Kang, Ashley, Weir, Nicola S, Meagher, Kyo, Farrington, Gregg S, Nelson, Prafull, Ghatage, Cheng-Han, Lee, Marjorie J, Riggan, Adelyn, Bolithon, Gordana, Popovic, Betty, Leung, Katrina, Tang, Neil, Lambie, Joshua, Millstein, Jennifer, Alsop, Michael S, Anglesio, Beyhan, Ataseven, Ellen, Barlow, Matthias W, Beckmann, Jessica, Berger, Christiani, Bisinotto, Hans, Bösmüller, Jessica, Boros, Alison H, Brand, Angela, Brooks-Wilson, Sara Y, Brucker, Michael E, Carney, Yovanni, Casablanca, Alicia, Cazorla-Jiménez, Paul A, Cohen, Thomas P, Conrads, Linda S, Cook, Penny, Coulson, Madeleine, Courtney-Brooks, Daniel W, Cramer, Philip, Crowe, Julie M, Cunningham, Cezary, Cybulski, Kathleen M, Darcy, Mona A, El-Bahrawy, Esther, Elishaev, Ramona, Erber, Rhonda, Farrell, Sian, Fereday, Anna, Fischer, María J, García, Simon A, Gayther, Aleksandra, Gentry-Maharaj, C Blake, Gilks, Marcel, Grube, Paul R, Harnett, Shariska Petersen, Harrington, Philipp, Harter, Arndt, Hartmann, Jonathan L, Hecht, Sebastian, Heikaus, Alexander, Hein, Florian, Heitz, Joy, Hendley, Brenda Y, Hernandez, Susanna Hernando, Polo, Sabine, Heublein, Akira, Hirasawa, Estrid, Høgdall, Claus K, Høgdall, Hugo M, Horlings, David G, Huntsman, Tomasz, Huzarski, Andrea, Jewell, Mercedes, Jimenez-Linan, Michael E, Jones, Scott H, Kaufmann, Catherine J, Kennedy, Dineo, Khabele, Felix K F, Kommoss, Roy F P M, Kruitwagen, Diether, Lambrechts, Nhu D, Le, Marcin, Lener, Jenny, Lester, Yee, Leung, Anna, Linder, Liselore, Loverix, Jan, Lubiński, Rashna, Madan, G Larry, Maxwell, Francesmary, Modugno, Susan L, Neuhausen, Alexander, Olawaiye, Siel, Olbrecht, Sandra, Orsulic, José, Palacios, Celeste Leigh, Pearce, Malcolm C, Pike, Carmel M, Quinn, Ganendra Raj, Mohan, Cristina, Rodríguez-Antona, Matthias, Ruebner, Andy, Ryan, Stuart G, Salfinger, Naoko, Sasamoto, Joellen M, Schildkraut, Minouk J, Schoemaker, Mitul, Shah, Raghwa, Sharma, Yurii B, Shvetsov, Naveena, Singh, Gabe S, Sonke, Linda, Steele, Colin J R, Stewart, Karin, Sundfeldt, Anthony J, Swerdlow, Aline, Talhouk, Adeline, Tan, Sarah E, Taylor, Kathryn L, Terry, Aleksandra, Tołoczko, Nadia, Traficante, Koen K, Van de Vijver, Maaike A, van der Aa, Toon, Van Gorp, Els, Van Nieuwenhuysen, Lilian, van-Wagensveld, Ignace, Vergote, Robert A, Vierkant, Chen, Wang, Lynne R, Wilkens, Stacey J, Winham, Anna H, Wu, Javier, Benitez, Andrew, Berchuck, Francisco J, Candido Dos Reis, Anna, DeFazio, Peter A, Fasching, Ellen L, Goode, Marc T, Goodman, Jacek, Gronwald, Beth Y, Karlan, Stefan, Kommoss, Usha, Menon, Hans-Peter, Sinn, Annette, Staebler, James D, Brenton, David D, Bowtell, Paul D P, Pharoah, Susan J, Ramus, Martin, Köbel, MUMC+: MA Obstetrie Gynaecologie (3), MUMC+: Vrouw Moeder en Kind Centrum (3), Obstetrie & Gynaecologie, MUMC+: MA Arts Assistenten Obstetrie Gynaecologie (6), RS: GROW - R2 - Basic and Translational Cancer Biology, and AOCS Group
Subjects: Cancer Research, ovarian cancer, Oncology, high-grade serous carcinoma, Human medicine, prognosis, CCNE1 amplification, cyclin E1 expression
Abstract: BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC. ispartof: CANCER vol:129 issue:5 pages:697-713 ispartof: location:United States status: published
Published: 2023

8. Profiling the immune landscape in mucinous ovarian carcinoma

Author: Nicola S. Meagher, Phineas Hamilton, Katy Milne, Shelby Thornton, Bronwyn Harris, Ashley Weir, Jennifer Alsop, Christiani Bisinoto, James D. Brenton, Angela Brooks-Wilson, Derek S. Chiu, Kara L. Cushing-Haugen, Sian Fereday, Dale W. Garsed, Simon A. Gayther, Aleksandra Gentry-Maharaj, Blake Gilks, Mercedes Jimenez-Linan, Catherine J. Kennedy, Nhu D. Le, Anna M. Piskorz, Marjorie J. Riggan, Mitul Shah, Naveena Singh, Aline Talhouk, Martin Widschwendter, David D.L. Bowtell, Francisco J. Candido dos Reis, Linda S. Cook, Renée T. Fortner, María J. García, Holly R. Harris, David G. Huntsman, Anthony N. Karnezis, Martin Köbel, Usha Menon, Paul D.P. Pharoah, Jennifer A. Doherty, Michael S. Anglesio, Malcolm C. Pike, Celeste Leigh Pearce, Michael L. Friedlander, Anna DeFazio, Brad H. Nelson, and Susan J. Ramus
Subjects: Ovarian Neoplasms, Lymphocytes, Tumor-Infiltrating, Oncology, Tumor Microenvironment, Humans, Obstetrics and Gynecology, Female, Forkhead Transcription Factors, Carcinoma, Ovarian Epithelial, CD8-Positive T-Lymphocytes, B7-H1 Antigen
Abstract: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients.We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration.Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates.In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.
Published: 2023

9. Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery

Author: Minh Tung Phung, Penelope M. Webb, Anna DeFazio, Sian Fereday, Alice W. Lee, David D.L. Bowtell, Peter A. Fasching, Ellen L. Goode, Marc T. Goodman, Beth Y. Karlan, Jenny Lester, Keitaro Matsuo, Francesmary Modugno, James D. Brenton, Toon Van Gorp, Paul D.P. Pharoah, Joellen M. Schildkraut, Karen McLean, Rafael Meza, Bhramar Mukherjee, Jean Richardson, Bronwyn Grout, Anne Chase, Cindy McKinnon Deurloo, Kathryn L. Terry, Gillian E. Hanley, Malcolm C. Pike, Andrew Berchuck, Susan J. Ramus, and Celeste Leigh Pearce
Subjects: Oncology, Obstetrics and Gynecology
Abstract: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery.This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS.Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53).The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.
Published: 2023

10. Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author: Nicola S, Meagher, Kylie L, Gorringe, Matthew, Wakefield, Adelyn, Bolithon, Chi Nam Ignatius, Pang, Derek S, Chiu, Michael S, Anglesio, Kylie-Ann, Mallitt, Jennifer A, Doherty, Holly R, Harris, Joellen M, Schildkraut, Andrew, Berchuck, Kara L, Cushing-Haugen, Ksenia, Chezar, Angela, Chou, Adeline, Tan, Jennifer, Alsop, Ellen, Barlow, Matthias W, Beckmann, Jessica, Boros, David D L, Bowtell, Alison H, Brand, James D, Brenton, Ian, Campbell, Dane, Cheasley, Joshua, Cohen, Cezary, Cybulski, Esther, Elishaev, Ramona, Erber, Rhonda, Farrell, Anna, Fischer, Zhuxuan, Fu, Blake, Gilks, Anthony J, Gill, Charlie, Gourley, Marcel, Grube, Paul R, Harnett, Arndt, Hartmann, Anusha, Hettiaratchi, Claus K, Høgdall, Tomasz, Huzarski, Anna, Jakubowska, Mercedes, Jimenez-Linan, Catherine J, Kennedy, Byoung-Gie, Kim, Jae-Weon, Kim, Jae-Hoon, Kim, Kayla, Klett, Jennifer M, Koziak, Tiffany, Lai, Angela, Laslavic, Jenny, Lester, Yee, Leung, Na, Li, Winston, Liauw, Belle W X, Lim, Anna, Linder, Jan, Lubiński, Sakshi, Mahale, Constantina, Mateoiu, Simone, McInerny, Janusz, Menkiszak, Parham, Minoo, Suzana, Mittelstadt, David, Morris, Sandra, Orsulic, Sang-Yoon, Park, Celeste Leigh, Pearce, John V, Pearson, Malcolm C, Pike, Carmel M, Quinn, Ganendra Raj, Mohan, Jianyu, Rao, Marjorie J, Riggan, Matthias, Ruebner, Stuart, Salfinger, Clare L, Scott, Mitul, Shah, Helen, Steed, Colin J R, Stewart, Deepak, Subramanian, Soseul, Sung, Katrina, Tang, Paul, Timpson, Robyn L, Ward, Rebekka, Wiedenhoefer, Heather, Thorne, Paul A, Cohen, Philip, Crowe, Peter A, Fasching, Jacek, Gronwald, Nicholas J, Hawkins, Estrid, Høgdall, David G, Huntsman, Paul A, James, Beth Y, Karlan, Linda E, Kelemen, Stefan, Kommoss, Gottfried E, Konecny, Francesmary, Modugno, Sue K, Park, Annette, Staebler, Karin, Sundfeldt, Anna H, Wu, Aline, Talhouk, Paul D P, Pharoah, Lyndal, Anderson, Anna, DeFazio, Martin, Köbel, Michael L, Friedlander, and Susan J, Ramus
Subjects: Ovarian Neoplasms, Cancer Research, BORDERLINE TUMORS, CARCINOMA, ADENOCARCINOMA, TRANSGELIN, Carcinoma, Ovarian Epithelial, EXPANSILE, Prognosis, INTESTINAL-TYPE, CANCER, Adenocarcinoma, Mucinous, PATTERN, RARE, Oncology, POOR-PROGNOSIS, Humans, Female, Neoplasm Staging, Gastrointestinal Neoplasms
Abstract: Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Published: 2022

11. Supplementary Figure 4 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Figure 4: Correlations between Methylation at CpG Sites and TAP1 mRNA Expression
Published: 2023

12. Supplementary Figure 1 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Figure 1: Methylation Signature Approximation
Published: 2023

13. Supplementary Grant Support from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar
Abstract: Supplementary Grant Support
Published: 2023

14. Supplementary Figure 2 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Figure 2: No Association between Methylation Signature and Baseline Clinical Factors
Published: 2023

15. Supplementary Table 6 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Table 6: Multivariate Modeling of Time to Recurrence/Death Among Studies with Gene Expression Data
Published: 2023

16. Supplementary Table 5 from Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition

Author: Kylie L. Gorringe, Ian G. Campbell, Kaylene J. Simpson, Richard B. Pearson, David G. Huntsman, David D.L. Bowtell, Susan J. Ramus, Felix Hilpert, Andreas du Bois, Jacobus Pfisterer, Stefan Kommoss, Anna Wu, Malcolm C. Pike, Celeste Leigh Pearce, Jacek Gronwald, Jan Lubinski, Aleksandra Gentry-Maharaj, Usha Menon, Maria P. Intermaggio, Sian Fereday, Nadia Traficante, Joshy George, Michael S. Anglesio, Karen E. Sheppard, and Sally J. Davis
Abstract: MetaCore analysis results
Published: 2023

17. Supplementary Figure 3 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Figure 3: Immune Analysis
Published: 2023

18. Supplementary Methods, Figures S1 - S3 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar
Abstract: Supplementary Figure S1. LocusZoom regional association plots for the seven new cross-cancer loci that were > 1 Mb from known index SNPs. Supplementary Figure S2A-B. Box plots showing eQTL associations between (A) rs9375701 and L3MBTL3 in normal breast and prostate tissues and (B) rs8037137 and RCCD1 in normal breast and ovarian tissues. Supplementary Figure S3. Interactions between BCL2L11 and the 32 Biocarta "Death Pathway" genes. Interactions were identified using the GeneMania server. Circles contain gene names, lines represent interactions, and the color of the line indicates a specific type of interaction as listed in the legend.
Published: 2023

19. Supplementary Tables S1 - S10 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar
Abstract: Supplementary Table S1. Known risk loci for each cancer. Supplementary Table S2. Regions where known index SNPs for at least two of the three cancers lie within 1 Mb of each other. Supplementary Table S3. Full results from the meta-analysis of breast, ovarian, and prostate cancer showing the 18 independent loci associated at P < 10-8 with the same direction of effect across all three cancers. Supplementary Table S4. Conditional analysis of the rs1469713 (breast-ovarian-prostate cancer) signal, conditioning on the rs4808801 (breast cancer-specific) signal that was < 1 Mb away using GCTA software. Supplementary Table S5. Most significantly-associated genotyped SNP at new loci where index SNPs were imputed. Supplementary Table S6. Expression QTL analysis results from the GTEx Portal for the new cross-cancer risk loci listed in main Table 2. Supplementary Table S7. SNPs with P < 10-8 at the new cross-cancer risk loci listed in main Table 2 that overlap predicted enhancers in at least two cell types. Supplementary Table S8. HaploReg and non-coding RNA annotation of variants with P < 10-8 at the new cross-cancer risk loci listed in main Table 2. Supplementary Table S9. Eight of the 32 genes involved in induction of apoptosis through DR3 and DR4/5 Death Receptors (MSigDB: Biocarta "Death Pathway") a that were < 1 Mb away from an independent P < 10-5 index SNP in the 3-cancer meta-analysis. Supplementary Table S10. INRICH pathway analysis results for pathways with empirical P < 0.05. Apoptosis-related pathways containing BCL2L11 are shaded.
Published: 2023

20. Supplementary Methods 1 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Methods 1: The original 60 CpG loci defining methylation-based subtypes, and the approximation method for methylation signature
Published: 2023

21. Supplementary Table 5 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Table 5: Modeling of Time to Recurrence/Death Among Studies with Gene Expression Data, excluding data from Previously Published Participants
Published: 2023

22. Data from Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition

Author: Kylie L. Gorringe, Ian G. Campbell, Kaylene J. Simpson, Richard B. Pearson, David G. Huntsman, David D.L. Bowtell, Susan J. Ramus, Felix Hilpert, Andreas du Bois, Jacobus Pfisterer, Stefan Kommoss, Anna Wu, Malcolm C. Pike, Celeste Leigh Pearce, Jacek Gronwald, Jan Lubinski, Aleksandra Gentry-Maharaj, Usha Menon, Maria P. Intermaggio, Sian Fereday, Nadia Traficante, Joshy George, Michael S. Anglesio, Karen E. Sheppard, and Sally J. Davis
Abstract: Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling. Mol Cancer Ther; 14(6); 1495–503. ©2015 AACR.
Published: 2023

23. Supplementary Table 4 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Table 4: Multivariate Modeling of Methylation Signature Among Studies with Multiple Datatypes
Published: 2023

24. Data from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Background:Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features.Methods:We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature that we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TIL), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1.Results:Methylation signature was associated with shorter time to recurrence, independent of clinical factors (N = 715 new set, hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.10–2.46; P = 0.015; N = 325 published set HR, 2.87; 95% CI, 2.17–3.81; P = 2.2 × 10−13) and remained prognostic after adjustment for gene expression molecular subtype and TAP1 expression (N = 599; HR, 2.22; 95% CI, 1.66–2.95; P = 4.1 × 10−8). Methylation signature was inversely related to CD8+ TIL levels (P = 2.4 × 10−7) and TAP1 expression (P = 0.0011) and was associated with gene expression molecular subtype (P = 5.9 × 10−4) in covariate-adjusted analysis.Conclusions:Multi-center analysis identified a novel quantitative tumor methylation signature of HGSC applicable to numerous commercially available platforms indicative of shorter time to recurrence/death, adjusting for other factors. Along with immune cell composition analysis, these results suggest a role for DNA methylation in the immunosuppressive microenvironment.Impact:This work aids in identification of targetable epigenome processes and stratification of patients for whom tailored treatment may be most beneficial.
Published: 2023

25. Supplementary Table 2 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Table 2: CpGs That Defined Previously Reported Methylation Subtypes Using a Semi-Supervised Clustering Approach
Published: 2023

26. Supplementary Table 1 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Author: Ellen L. Goode, Stacey J. Winham, David D. Bowtell, Jesus Gonzalez Bosquet, Tanja Pejovic, Martin Widschwendter, Michael S. Anglesio, Dinuka Ariyaratne, Jennifer A. Doherty, Sian Fereday, Dale W. Garsed, Brooke D. Jorgensen, Martin Köbel, Nadja Pejovic, Susan J. Ramus, Aline Talhouk, Nadia Traficante, Robert A. Vierkant, Sebastian M. Armasu, Bryan M. McCauley, Mark E. Sherman, Julie M. Cunningham, Matthew S. Block, and Chen Wang
Abstract: Supplementary Table 1: Characteristics of Study Participants with High Grade Serous Tubo-Ovarian Carcinoma by Contributing Study
Published: 2023

27. Supplementary Tables 1 - 4 from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author: Ellen L. Goode, Keith L. Knutson, Lara E. Sucheston, Kunle Odunsi, Roberta B. Ness, Simon A. Gayther, Paul D.P. Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel W. Cramer, Celeste Leigh Pearce, Joellen M. Schildkraut, Usha Menon, Susanne K. Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas Wentzensen, Jolanta Kupryjanczyk, Jenny Chang-Claude, Elisa V. Bandera, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Gottfried Konecny, Peter A. Fasching, Ian Campbell, Marc T. Goodman, Tanja Pejovic, Yukie T. Bean, Laura E. Hays, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W. Beckmann, Arif B. Ekici, James Paul, Robert Brown, James M. Flanagan, Philipp Harter, Andreas du Bois, Ira Schwaab, Claus K. Hogdall, Sara H. Olson, Lene Lundvall, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Petra Seibold, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Beata Spiewankiewicz, Louise A. Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubiński, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Howard Shen, Brenda Diergaarde, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van Den Berg, Kathryn L. Terry, Allison F. Vitonis, Starr M. Ramirez, Thomas A. Sellers, Catherine M. Phelan, Jennifer A. Doherty, Sharon E. Johnatty, Anna deFazio, Honglin Song, Jonathan Tyrer, Chen Wang, Kate Lawrenson, Lynn C. Hartmann, Claudia Preston, David N. Rider, Julie M. Cunningham, Brooke L. Fridley, Krista M. Goergen, Matthew J. Maurer, Matthew S. Block, Zachary C. Fogarty, Robert A. Vierkant, Ann L. Oberg, Kimberly R. Kalli, Kirsten B. Moysich, and Bridget Charbonneau
Abstract: PDF file - 157K, Supplemental Table 1. Regulatory T cell genes included in this study (N=25). Supplemental Table 2. Regulatory T cell SNPs included in this study. Supplemental Table 3. Participating invasive epithelial ovarian cancer studies. Supplemental Table 4. Association between clinical variables and overall survival.
Published: 2023

28. Supplementary Table 1 from Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition

Author: Kylie L. Gorringe, Ian G. Campbell, Kaylene J. Simpson, Richard B. Pearson, David G. Huntsman, David D.L. Bowtell, Susan J. Ramus, Felix Hilpert, Andreas du Bois, Jacobus Pfisterer, Stefan Kommoss, Anna Wu, Malcolm C. Pike, Celeste Leigh Pearce, Jacek Gronwald, Jan Lubinski, Aleksandra Gentry-Maharaj, Usha Menon, Maria P. Intermaggio, Sian Fereday, Nadia Traficante, Joshy George, Michael S. Anglesio, Karen E. Sheppard, and Sally J. Davis
Abstract: Nanostring data including clinical information
Published: 2023

29. Data from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author: Ellen L. Goode, Keith L. Knutson, Lara E. Sucheston, Kunle Odunsi, Roberta B. Ness, Simon A. Gayther, Paul D.P. Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel W. Cramer, Celeste Leigh Pearce, Joellen M. Schildkraut, Usha Menon, Susanne K. Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas Wentzensen, Jolanta Kupryjanczyk, Jenny Chang-Claude, Elisa V. Bandera, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Gottfried Konecny, Peter A. Fasching, Ian Campbell, Marc T. Goodman, Tanja Pejovic, Yukie T. Bean, Laura E. Hays, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W. Beckmann, Arif B. Ekici, James Paul, Robert Brown, James M. Flanagan, Philipp Harter, Andreas du Bois, Ira Schwaab, Claus K. Hogdall, Sara H. Olson, Lene Lundvall, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Petra Seibold, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Beata Spiewankiewicz, Louise A. Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubiński, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Howard Shen, Brenda Diergaarde, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van Den Berg, Kathryn L. Terry, Allison F. Vitonis, Starr M. Ramirez, Thomas A. Sellers, Catherine M. Phelan, Jennifer A. Doherty, Sharon E. Johnatty, Anna deFazio, Honglin Song, Jonathan Tyrer, Chen Wang, Kate Lawrenson, Lynn C. Hartmann, Claudia Preston, David N. Rider, Julie M. Cunningham, Brooke L. Fridley, Krista M. Goergen, Matthew J. Maurer, Matthew S. Block, Zachary C. Fogarty, Robert A. Vierkant, Ann L. Oberg, Kimberly R. Kalli, Kirsten B. Moysich, and Bridget Charbonneau
Abstract: The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22–1.64; P = 5.7 × 10−6], rs791587 (HR, 1.36; 95% CI, 1.17–1.57; P = 6.2 × 10−5), rs2476491 (HR, = 1.40; 95% CI, 1.19–1.64; P = 5.6 × 10−5), and rs10795763 (HR, 1.35; 95% CI, 1.17–1.57; P = 7.9 × 10−5), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54–0.82; P = 9.3 × 10−5) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR.
Published: 2023

30. Supplementary Figures and Tables from Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition

Author: Kylie L. Gorringe, Ian G. Campbell, Kaylene J. Simpson, Richard B. Pearson, David G. Huntsman, David D.L. Bowtell, Susan J. Ramus, Felix Hilpert, Andreas du Bois, Jacobus Pfisterer, Stefan Kommoss, Anna Wu, Malcolm C. Pike, Celeste Leigh Pearce, Jacek Gronwald, Jan Lubinski, Aleksandra Gentry-Maharaj, Usha Menon, Maria P. Intermaggio, Sian Fereday, Nadia Traficante, Joshy George, Michael S. Anglesio, Karen E. Sheppard, and Sally J. Davis
Abstract: Supplementary Figures S1 (Nanostring data and combined PFS for BMP8B and ATP13A4), S2 (Nanostring expression histograms), S3 (GAB2 survival by cohort), S4 (BMP8B and ATP13A4 survival by cohort), S5 (Metacore network maps); Supplementary Tables S2 (Cell line information), S3 (Univariate survival analysis results), S4 (Step-wise AIC results) and S6 (association of GAB2 expression with PRAS40).
Published: 2023

31. Supplementary Methods 1 from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author: Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher
Abstract: Supplementary Methods
Published: 2023

32. Supplementary Figures S1-S13 from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author: Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher
Abstract: Supplementary Figures S1-S13
Published: 2023

33. Data from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author: Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher
Abstract: Purpose:Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental Design:Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).Results:Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).Conclusions:An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Published: 2023

34. Supplementary Tables S1-S11 from Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Author: Susan J. Ramus, Michael L. Friedlander, Martin Köbel, Anna DeFazio, Lyndal Anderson, Paul D.P. Pharoah, Aline Talhouk, Anna H. Wu, Karin Sundfeldt, Annette Staebler, Sue K. Park, Francesmary Modugno, Gottfried E. Konecny, Stefan Kommoss, Linda E. Kelemen, Beth Y. Karlan, Paul A. James, David G. Huntsman, Estrid Høgdall, Nicholas J. Hawkins, Jacek Gronwald, Peter A. Fasching, Philip Crowe, Paul A. Cohen, Heather Thorne, Rebekka Wiedenhoefer, Robyn L. Ward, Paul Timpson, Katrina Tang, Soseul Sung, Deepak Subramanian, Colin J.R. Stewart, Helen Steed, Mitul Shah, Clare L. Scott, Stuart Salfinger, Matthias Ruebner, Marjorie J. Riggan, Jianyu Rao, Ganendra Raj Mohan, Carmel M. Quinn, Malcolm C. Pike, John V. Pearson, Celeste Leigh Pearce, Sang-Yoon Park, Sandra Orsulic, David Morris, Suzana Mittelstadt, Parham Minoo, Janusz Menkiszak, Simone McInerny, Constantina Mateoiu, Sakshi Mahale, Jan Lubiński, Anna Linder, Belle W.X. Lim, Winston Liauw, Na Li, Yee Leung, Jenny Lester, Angela Laslavic, Tiffany Lai, Jennifer M. Koziak, Kayla Klett, Jae-Hoon Kim, Jae-Weon Kim, Byoung-Gie Kim, Catherine J. Kennedy, Mercedes Jimenez-Linan, Anna Jakubowska, Tomasz Huzarski, Claus K. Høgdall, Anusha Hettiaratchi, Arndt Hartmann, Paul R. Harnett, Marcel Grube, Charlie Gourley, Anthony J. Gill, Blake Gilks, Zhuxuan Fu, Anna Fischer, Rhonda Farrell, Ramona Erber, Esther Elishaev, Cezary Cybulski, Joshua Cohen, Dane Cheasley, Ian Campbell, James D. Brenton, Alison H. Brand, David D.L. Bowtell, Jessica Boros, Matthias W. Beckmann, Ellen Barlow, Jennifer Alsop, Adeline Tan, Angela Chou, Ksenia Chezar, Kara L. Cushing-Haugen, Andrew Berchuck, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Kylie-Ann Mallitt, Michael S. Anglesio, Derek S. Chiu, Chi Nam Ignatius Pang, Adelyn Bolithon, Matthew Wakefield, Kylie L. Gorringe, and Nicola S. Meagher
Abstract: Supplementary Tables S1-S11
Published: 2023

35. Table S8 from A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author: Jirong Long, Wei Zheng, Paul D.P. Pharoah, Thomas A. Sellers, Georgia Chenevix-Trench, Ellen L. Goode, Andrew Berchuck, Antonis C. Antoniou, Simon A. Gayther, Kristin K. Zorn, Drakoulis Yannoukakos, Anna H. Wu, Alicja Wolk, Emily White, Nicolas Wentzensen, Jeffrey N. Weitzel, Penelope M. Webb, Digna Velez Edwards, Ana Vega, Adriaan Vanderstichele, Elizabeth J. van Rensburg, Shelley S. Tworoger, Nadine Tung, Antonia Trichopoulou, Amanda E. Toland, Marc Tischkowitz, Mads Thomassen, Soo H. Teo, Manuel R. Teixeira, Anthony J. Swerdlow, Rebecca Sutphen, Amanda B. Spurdle, Melissa C. Southey, Honglin Song, Christian F. Singer, Jacques Simard, Weiva Sieh, Priyanka Sharma, Veronica W. Setiawan, Rita K. Schmutzler, Dale P. Sandler, Iwona K. Rzepecka, Mary Anne Rossing, Matti A. Rookus, Isabelle Romieu, Cristina Rodríguez-Antona, Gustavo C. Rodriguez, Harvey Risch, Gad Rennert, Susan J. Ramus, Miquel Angel Pujana, Catherine M. Phelan, Paolo Peterlongo, Tanja Pejovic, Petra H.M. Peeters, Michael T. Parsons, Sue K. Park, Ana Osorio, Håkan Olsson, Sara H. Olson, Olufunmilayo I. Olopade, Edith Olah, Kenneth Offit, Robert L. Nussbaum, Liene Nikitina-Zake, Finn C. Nielsen, Heli Nevanlinna, Susan L. Neuhausen, Marco Montagna, Francesmary Modugno, Melissa A. Merritt, Iain A. McNeish, Lesley McGuffog, Taymaa May, Amalia Mattiello, Douglas A. Levine, Fabienne Lesueur, Goska Leslie, Nhu D. Le, Ava Kwong, Susanne K. Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Beth Y. Karlan, Paul James, Anna Jakubowska, Claudine Isaacs, Evgeny N. Imyanitov, David G. Huntsman, Peter J. Hulick, Antoinette Hollestelle, Claus K. Høgdall, Michelle A.T. Hildebrandt, Florian Heitz, Ute Hamann, Jacek Gronwald, Mark H. Greene, Marc T. Goodman, David E. Goldgar, Andrew K. Godwin, Graham G. Giles, Judy Garber, Patricia A. Ganz, Eitan Friedman, George Fountzilas, Renée T. Fortner, Peter A. Fasching, Diana M. Eccles, Douglas F. Easton, Thilo Dörk, Susan M. Domchek, Orland Diez, Joe Dennis, Anna deFazio, Mary B. Daly, Daniel W. Cramer, Fergus J. Couch, Kathleen B.M. Claes, Jenny Chang-Claude, Ian Campbell, Maria A. Caligo, Trinidad Caldes, Ralf Butzow, James Brenton, Line Bjorge, Javier Benitez, Daniel R. Barnes, Rosa B. Barkardottir, Elisa V. Bandera, Banu K. Arun, Hoda Anton-Culver, Irene L. Andrulis, Kirsten B. Moysich, Jamie K. Teer, Brett M. Reid, Jennifer B. Permuth, Yian A. Chen, Hae Kyung Im, Joellen M. Schildkraut, Bingshan Li, Xingyi Guo, Lang Wu, Alicia Beeghly-Fadiel, and Yingchang Lu
Abstract: Association results between minor alleles of 467 variants incorportated in cross tissue gene expression prediction model for the gene of CRHR1.
Published: 2023

36. Data from Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Author: Paul D.P. Pharoah, Simon A. Gayther, Matthew L. Freedman, Alvaro N.A. Monteiro, Thomas A. Sellers, Argyrios Ziogas, Wei Zheng, Hannah Yang, Anna Wu, Xifeng Wu, Yin-Ling Woo, Lynne R. Wilkens, Kristine G. Wicklund, Alice S. Whittemore, Nicolas Wentzensen, Christine Walsh, Shan Wang-Gohrke, Robert A. Vierkant, Ignace Vergote, Els Van Nieuwenhuysen, Anne M. van Altena, Shelley S. Tworoger, Ya-Yu Tsai, Agnieszka Timorek, Pamela J. Thompson, Kathryn L. Terry, Soo-Hwang Teo, Ingvild L. Tangen, Lara E. Sucheston-Campbell, Melissa C. Southey, Honglin Song, Weiva Sieh, Nadeem Siddiqui, Yurii B. Shvetsov, Xiao-Ou Shu, Ira Schwaab, Joellen M. Schildkraut, Helga B. Salvesen, Iwona K. Rzepecka, Ingo B. Runnebaum, Anja Rudolph, Joseph H. Rothstein, Mary Anne Rossing, Barry Rosen, Harvey A. Risch, Susan J. Ramus, Elizabeth M. Poole, Malcolm C. Pike, Catherine M. Phelan, Jennifer Permuth-Wey, Liisa M. Pelttari, Tanja Pejovic, Celeste Leigh Pearce, Rachel Palmieri Weber, Sandra Orsulic, Irene Orlow, Sara H. Olson, Kunle Odunsi, Heli Nevanlinna, Roberta B. Ness, Lotte Nedergaard, Steven A. Narod, Kirsten B. Moysich, Francesmary Modugno, Usha Menon, Iain A. McNeish, John R. McLaughlin, Valerie McGuire, Keitaro Matsuo, Leon Massuger, Lene Lundvall, Jan Lubinski, Karen Lu, Jolanta Lissowska, Dong Liang, Douglas A. Levine, Jenny Lester, Arto Leminen, Shashi Lele, Alice W. Lee, Nhu D. Le, Sandrina Lambrechts, Diether Lambrechts, Jolanta Kupryjanczyk, Camilla Krakstad, Lambertus A. Kiemeney, Joseph Kelley, Melissa Kellar, Linda E. Kelemen, Susanne K. Kjaer, Beth Y. Karlan, Bu-Tian Ji, Allan Jensen, James Paul, Anna Jakubowska, Edwin S. Iversen, Satoyo Hosono, Claus K. Hogdall, Estrid Hogdall, Peter Hillemanns, Michelle A.T. Hildebrandt, Florian Heitz, Alexander Hein, Philipp Harter, Patricia Harrington, Jacek Grownwald, Marc T. Goodman, Ellen L. Goode, Rosalind Glasspool, Graham G. Giles, Aleksandra Gentry-Maharaj, Yu-Tang Gao, Brooke L. Fridley, Peter A. Fasching, Arif B. Ekici, Robert P. Edwards, Douglas F. Easton, Diana Eccles, Matthias Dürst, Andreas du Bois, Thilo Dörk, Jennifer A. Doherty, Ed Dicks, Joe Dennis, Agnieszka Dansonka-Mieszkowska, Cezary Cybulski, Julie M. Cunningham, Daniel Cramer, Linda S. Cook, Zhihua Chen, Yian Ann Chen, Jenny Chang-Claude, Karen Carty, Ian Campbell, Ralf Butzow, Angela Brooks-Wilson, Louise Brinton, Natalia Bogdanova, Line Bjørge, Maria Bisogna, Andrew Berchuck, Matthias W. Beckmann, Yukie T. Bean, Elisa V. Bandera, Helen Baker, Georgia Chenevix-Trench, Natalia Antonenkova, Hoda Anton-Culver, Katja K.H. Aben, Kate Lawrenson, Qiyuan Li, Jonathan P. Tyrer, and Siddhartha P. Kar
Abstract: Background: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.Methods: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).Results: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.Conclusion: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.Impact: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. Cancer Epidemiol Biomarkers Prev; 24(10); 1574–84. ©2015 AACR.
Published: 2023

37. Supplementary Table S1 from Effects of Common Germ-Line Genetic Variation in Cell Cycle Genes on Ovarian Cancer Survival

Author: Simon A. Gayther, Paul D.P. Pharoah, Susanne Kruger Kjaer, Douglas F. Easton, David Greenberg, Mitul Shah, Alice S. Whittemore, Valerie McGuire, Lydia Quaye, Claus Hogdall, Richard A. DiCioccio, Susan J. Ramus, Estrid Hogdall, and Honglin Song
Abstract: Supplementary Table S1 from Effects of Common Germ-Line Genetic Variation in Cell Cycle Genes on Ovarian Cancer Survival
Published: 2023

38. Figure S3 from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author: Ellen L. Goode, Thomas A. Sellers, Brooke L. Fridley, Paul D.P. Pharoah, Catherine M. Phelan, Jennifer Permuth-Wey, Joellen M. Schildkraut, Andrew Berchuck, Argyrios Ziogas, Hannah Yang, Anna H. Wu, Lynne R. Wilkens, Christine Walsh, Allison F. Vitonis, Robert A. Vierkant, David J. van den Berg, Jonathan P. Tyrer, Pamela J. Thompson, Kathryn L. Terry, Honglin Song, Susan J. Ramus, Malcolm C. Pike, Irene Orlow, Kirsten B. Moysich, Francesmary Modugno, Janusz Menkiszak, Jan Lubinski, Jolanta Lissowska, Hui-Yi Lin, Jenny Lester, Sharon E. Johnatty, Allan Jensen, Edwin S. Iversen, Martin Gore, Aleksandra Gentry-Maharaj, Simon A. Gayther, Robert P. Edwards, Ed M. Dicks, Anna deFazio, Cezary Cybulski, Julie M. Cunningham, Michael E. Carney, Louise A. Brinton, Maria Bisogna, Yukie T. Bean, Nicolas Wentzensen, Mary Anne Rossing, Tanja Pejovic, Celeste L. Pearce, Roberta B. Ness, Usha Menon, Douglas A. Levine, Susanne K. Kjaer, Beth Y. Karlan, Jacek Gronwald, Marc T. Goodman, Jennifer A. Doherty, Daniel Cramer, Elisa V. Bandera, Hoda Anton-Culver, Madalene A. Earp, Zachary C. Fogarty, Melissa C. Larson, Yian Ann Chen, Ailith Pirie, and Stacey J. Winham
Abstract: Supplemental Figure S 3
Published: 2023

39. Supplementary Figures 1-4 and extended methods from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author: Alvaro N.A. Monteiro, Simon A. Gayther, Paul D. Pharoah, Ellen L. Goode, Thomas A. Sellers, Timothy R. Hughes, Houtan Noushmehr, Gerhard A. Coetzee, Catherine M. Phelan, Susan J. Ramus, Georgia Chenevix-Trench, Harvey Risch, Sean J. Yoder, Madalene A. Earp, Ally W. Yang, Howard C. Shen, Simon G. Coetzee, Paulo C. Lyra, Renato S. Carvalho, Anxhela Gjyshi, Hamed S. Najafabadi, Dennis J. Hazelett, Kate Lawrenson, Gustavo Mendoza-Fandiño, Jonathan P. Tyrer, Nicholas T. Woods, and Melissa A. Buckley
Abstract: This file contains: Supplementary Figure 1 (Related to Figure 2): Haplotype frequency for tiles Enhancer Scanning times with multiple SNPs. Supplementary Figure 2 (Related to Figure 3): Conservation and S/MAR predicted sequences at the locus. Supplementary Figure 3: Study overview and Overlap between the set of 134 SNPs obtained through the LD-guided analysis and the set of 40 SNPs obtained through the fine mapping-guided approach. Supplementary Figure 4 (Related to Figure 5): BNC2 binds to its own promoter. Extended data and detailed methods (including QC metrics) for BNC2 ChIP-Seq.
Published: 2023

40. Supplementary Tables 1-4 from Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Jacques Simard, Kenneth Offit, Georgia Chenevix-Trench, Douglas F. Easton, Phuong L. Mai, Mark H. Greene, Paolo Radice, Liliana Varesco, Giuseppe Giannini, Alessandra Viel, Loris Bernard, Monica Barile, Daniela Zaffaroni, Bernard Peissel, Siranoush Manoukian, Paolo Peterlongo, V. Shane Pankratz, Zachary Fredericksen, Noralane M. Lindor, Yuan Chun Ding, Susan L. Neuhausen, Amanda B. Spurdle, Marc D. Tischkowitz, Heli Nevanlinna, Taru A. Muranen, Miguel de la Hoya, Trinidad Caldes, Wolfram Heinritz, Britta Fiebig, Karin Kast, Christian Sutter, Andrea Gehrig, Helmut Deissler, Raymonda Varon-Mateeva, Dorothea Gadzicki, Sabine Preisler-Adams, Dieter Niederacher, Simone Heidemann, Norbert Arnold, Nina Ditsch, Alfons Meindl, Christoph Engel, Barbara Wappenschmidt, Rita K. Schmutzler, Ava Kwong, Orland Diez, Cecelia M. Dorfling, Elizabeth J. van Rensburg, Mary S. Beattie, Patricia A. Ganz, Soo Hwang Teo, Edith Olah, Christine S. Walsh, Beth Y. Karlan, Kunle O. Odunsi, Paul P.D. Pharoah, Simon A. Gayther, Joan Brunet, Lidia Feliubadalo, Ignacio Blanco, Conxi Lazaro, Ramunas Janavicius, Claudine Isaacs, Evgeny N. Imyanitov, Simona Agata, Marco Montagna, Amanda Ewart-Toland, Katie Wakeley, John Boggess, Wendy S. Rubinstein, Jack Basil, Kelly Phillips, Marion Piedmonte, Mark E. Robson, Kara Sarrel, Sohela Shah, Joseph Vijai, Aðalgeir Arason, Finn C. Nielsen, Thomas V.O. Hansen, Anneliese Fink-Retter, Muy-Kheng M. Tea, Christine Rappaport, Christian F. Singer, David E. Goldgar, John L. Hopper, Melissa C. Southey, Alexander Miron, Esther M. John, Wendy K. Chung, MaryBeth Terry, Mary B. Daly, Saundra S. Buys, Carrie L. Snyder, Henry T. Lynch, Linda Akloul, Capucine Delnatte, Isabelle Coupier, Pascal Pujol, Olivier Caron, Brigitte Bressac-de Paillerets, Nadia Boutry-Kryza, Mélanie Léoné, Sylvie Mazoyer, François Cornelis, Laurent Castera, Marion Fassy-Colcombet, Dominique Stoppa-Lyonnet, Andrew K. Godwin, Betsy Bove, Lucy E. Side, M. John Kennedy, Mary E. Porteous, Lisa Walker, Patrick J. Morrison, Shirley V. Hodgson, Fiona Douglas, Carole Brewer, Joan Paterson, Jackie Cook, Trevor Cole, Diana M. Eccles, Rosemarie Davidson, Julian Adlard, Rosalind A. Eeles, Chris Jacobs, D. Gareth Evans, Elena Fineberg, Radka Platte, Steve D. Ellis, Debra Frost, Susan Peock, Margreet G.E.M. Ausems, Rogier A. Oldenburg, Maartje J. Hooning, Marleen Kets, Marinus J. Blok, Juul Wijnen, Hanne E.J. Meijers-Heijboer, Flora E. van Leeuwen, Theo A. van Os, Frans B.L. Hogervorst, Ute Hamann, Javier Benitez, María Isabel Tejada, Mercedes Durán, Ana Osorio, Bohdan Górski, Cezary Cybulski, Jacek Gronwald, Tomasz Byrski, Tomasz Huzarski, Elżbieta Złowocka, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Ania Jakubowska, Susan M. Domchek, Timothy R. Rebbeck, Katherine L. Nathanson, Per Karlsson, Hans Ehrencrona, Maria Soller, Niklas Loman, Gisela Barbany-Bustinza, Anna von Wachenfeldt, Maria A. Caligo, Torben A. Kruse, Anne-Bine Skytte, Uffe Birk Jensen, Anne-Marie Gerdes, Mads Thomassen, Anna Marie Mulligan, Hilmi Ozcelik, Irene L. Andrulis, Olga M. Sinilnikova, Sue Healey, Andrew Lee, Daniel Barrowdale, Lesley McGuffog, Tomas Kirchhoff, Xianshu Wang, Xiaoqing Chen, Jonathan Beesley, Penny Soucy, Karoline B. Kuchenbaecker, Susan J. Ramus, Antonis C. Antoniou, Mia M. Gaudet, and Fergus J. Couch
Abstract: PDF file - 90K
Published: 2023

41. Supplementary Material and Method from Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer

Author: John A. Martignetti, Peter Dottino, Morten Mau-Sørensen, Mansoor R. Mirza, Michael Kauffman, Tami Rashal, Yosef Landesman, Dilara McCauley, Sharon Shacham, Jean-Noel Billaud, Richard Halpert, Rileen Sinha, Rong Chen, Andrew Uzilov, Robert Sebra, Tamara Kalir, Faisal Khan, Michael Donovan, Estefania Rodriguez, Nolan Priedigkeit, Fei Huang, Susan J. Ramus, Brad R. Evans, Elena Pereira, Eva Kalir, John F. Gerecitano, Nashat Y. Gabrail, Albiruni R.A. Razak, Thomas R. Silvers, Sandra Catalina Camacho, and Ying Chen
Abstract: Supplementary Material and Method
Published: 2023

42. Data from Predicting Clinical Outcome in Patients Diagnosed with Synchronous Ovarian and Endometrial Cancer

Author: Simon A. Gayther, John C. Whittaker, Ian J. Jacobs, W. Glenn McCluggage, Naveena Singh, Ayse Ayhan, Karen Lu, Alex Gammerman, Zhiyuan Luo, Karim Elmasry, and Susan J. Ramus
Abstract: Purpose: Patients with synchronous ovarian and endometrial cancers may represent cases of a single primary tumor with metastasis (SPM) or dual primary tumors (DP). The diagnosis given will influence the patient's treatment and prognosis. Currently, a diagnosis of SPM or DP is made using histologic criteria, which are frequently unable to make a definitive diagnosis.Experimental Design: In this study, we used genetic profiling to make a genetic diagnosis of SPM or DP in 90 patients with synchronous ovarian/endometrial cancers. We compared genetic diagnoses in these patients with the original histologic diagnoses and evaluated the clinical outcome in this series of patients based on their diagnoses.Results: Combining genetic and histologic approaches, we were able make a diagnosis in 88 of 90 cases, whereas histology alone was able to make a diagnosis in only 64 cases. Patients diagnosed with SPM had a significantly worse survival than patients with DP (P = 0.002). Patients in which both tumors were of endometrioid histology survived longer than patients of other histologic subtypes (P = 0.025), and patients diagnosed with SPM had a worse survival if the mode of spread was from ovary to endometrium rather than from endometrium to ovary (P = 0.019).Conclusions: Genetic analysis may represent a powerful tool for use in clinical practice for distinguishing between SPM and DP in patients with synchronous ovarian/endometrial cancer and predicting disease outcome. The data also suggest a hitherto uncharacterized level of heterogeneity in these cases, which, if accurately defined, could lead to improved treatment and survival.
Published: 2023

43. Data from Effects of Common Germ-Line Genetic Variation in Cell Cycle Genes on Ovarian Cancer Survival

Author: Simon A. Gayther, Paul D.P. Pharoah, Susanne Kruger Kjaer, Douglas F. Easton, David Greenberg, Mitul Shah, Alice S. Whittemore, Valerie McGuire, Lydia Quaye, Claus Hogdall, Richard A. DiCioccio, Susan J. Ramus, Estrid Hogdall, and Honglin Song
Abstract: Purpose: Somatic alterations have been shown to correlate with ovarian cancer prognosis and survival, but less is known about the effects on survival of common inherited genetic variation. Of particular interest are genes involved in cell cycle pathways, which regulate cell division and could plausibly influence clinical characteristics of multiple tumors types.Experimental Design: We examined associations between common germ-line genetic variation in 14 genes involved in cell cycle pathway (CCND1, CCND2, CCND3, CCNE1, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CDK2, CDK4, CDK6, and RB1) and survival among women with invasive ovarian cancer participating in a multicenter case-control study from United Kingdom, Denmark, and United States. DNAs from up to 1,499 women were genotyped for 97 single-nucleotide polymorphisms that tagged the known common variants (minor allele frequency ≥0.05) in these genes. The genotypes of each polymorphism were tested for association with survival by Cox regression analysis.Results: A nominally statistically significant association between genotype and ovarian cancer survival was observed for polymorphisms in CCND2 and CCNE1. The per-allele hazard ratios (95% confidence intervals) were 1.16 (1.03-1.31; P = 0.02) for rs3217933, 1.14 (1.02-1.27; P = 0.024) for rs3217901, and 0.85 (0.73-1.00; P = 0.043) for rs3217862 in CCND2 and 1.39 (1.04-1.85; P = 0.033) for rs3218038 in CCNE1. However, these were not significant after adjusting for multiple hypothesis tests.Conclusion: It is unlikely that common variants in cell cycle pathways examined above associated with moderate effect in survival after diagnosis of ovarian cancer. Much larger studies will be needed to exclude common variants with small effects.
Published: 2023

44. Supplementary Tables 1 - 4 from Common Breast Cancer Susceptibility Variants in LSP1 and RAD51L1 Are Associated with Mammographic Density Measures that Predict Breast Cancer Risk

Author: Isabel dos-Santos-Silva, John L. Hopper, V. Shane Pankratz, Anna H. Wu, Tina Audley, Kamila Czene, Louise Eriksson, JianJun Liu, Edyta Reszka, Agnieszka Bukowska, Beata Peplonska, Ewa Wesolowska, Jolanta Lissowska, Jonine D. Figuero, Norman F. Boyd, Julia A. Knight, Irene L. Andrulis, David J. Hunter, Susan E. Hankinson, Sara Lindström, Anne-Lise Børresen-Dale, Vessela N. Kristensen, Inger Torhild Gram, Grethe I.G. Alnaes, Margarethe Biong, Valeria A. McCormack, Nichola Johnson, Kate Walker, Christopher A. Haiman, Gertraud Maskarinec, Christy Woolcott, Laurence N. Kolonel, Loic Le Marchand, Melissa C. Southey, Kavitha Krishnan, Laura Baglietto, Graham G. Giles, Fergus J. Couch, Gek Kwan-Lim, Martin O. Leach, Rosalind A. Eeles, Susan J. Ramus, Simon A. Gayther, Eunjung Lee, Giske Ursin, Kay-Tee Khaw, Ruth J.F. Loos, Nicholas J. Wareham, Ruth M.L. Warren, Robert N. Luben, Deborah J. Thompson, Douglas F. Easton, Jajini S. Varghese, Jean Leyland, Judith Brown, Petra H.M. Peeters, N. Charlotte Onland-Moret, Mariëtte Lokate, Carla H. van Gils, Javier Benitez, Anna Gonzalez-Neira, Pablo Fernández-Navarro, Marina Pollan, Matthias W. Beckmann, Katharina Heusinger, Sebastian M. Jud, Gretchen L. Gierach, Fabrice Odefrey, Carmel Apicella, Jennifer Stone, Jingmei Li, Rulla M. Tamimi, Per Hall, Peter A. Fasching, Christopher G. Scott, and Celine M. Vachon
Abstract: PDF file, 120KB, Supplemental Table 1. Study Descriptions, Design and Sample Size for 19 DENSNP Studies. Caucasian Women Only. Supplemental Table 2. Source and Timing of Reproductive and Anthropometric Variable Collection. Supplemental Table 3. Description of Mammogram View, Side, Film Digitizer and Density Estimation Software for DENSNP Studies. Supplemental Table 4. Genotyping Platform and SNP Call Rates Performed by Each Study.
Published: 2023

45. Supplementary Figures 1-5, Tables 1-8 from Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Author: Georgia Chenevix-Trench, Penelope M. Webb, Anna deFazio, Ellen L. Goode, Paul D.P. Pharoah, Stuart MacGregor, Andrew Berchuck, Yoke-Eng Chiew, Catherine Kennedy, Thomas Sellers, Rosalind Glasspool, Nadeem Siddiqui, Karen Carty, James Paul, Ian McNeish, Lene Lundvall, Claus Høgdall, Yukie Bean, Tanja Pejovic, Irene Orlow, Elisa V. Bandera, Daniel W. Cramer, Kathryn L. Terry, Edwin S. Iversen, Joellen M. Schildkraut, Robert A. Vierkant, Julie M. Cunningham, Brooke L. Fridley, Susanne Kruger Kjaer, Allan Jensen, Estrid Høgdall, Zachary C. Fogarty, Melissa C. Larson, Madalene Earp, Stacey J. Winham, Sandra Orsulic, Jenny Lester, Christine Walsh, Beth Y. Karlan, Peter Hillemanns, Jacobus Pisterer, Philipp Harter, Ira Schwaab, Andreas du Bois, Florian Heitz, Pamela J. Thompson, Michael E. Carney, Lynne R. Wilkens, Marc T. Goodman, Beata Spiewankiewicz, Iwona K. Rzepecka, Agnieszka Dansonka-Mieszkowska, Jolanta Kupryjanczyk, Anna H. Wu, Daniel O. Stram, Malcolm C. Pike, Celeste L. Pearce, Susan J. Ramus, Usha Menon, Aleksandra Gentry-Maharaj, Simon A. Gayther, Argyrios Ziogas, Hoda Anton-Culver, Rebecca Sutphen, Joseph H. Rothstein, Valerie McGuire, Alice S. Whittemore, Weiva Sieh, Diana Eccles, Ian Campbell, Valerie Rhenius, Honglin Song, Nicolas Wentzensen, Jolanta Lissowska, Louise Brinton, Cezary Cybulski, Anna Jakubowska, Jan Lubiński, Jacek Gronwald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Douglas A. Levine, Kirsten B. Moysich, Roberta B. Ness, Francesmary Modugno, Jenny Chang-Claude, Jennifer A. Doherty, Mary Anne Rossing, Sandrina Lambrechts, Ignace Vergote, Els Van Nieuwenhuysen, Diether Lambrechts, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Peter A. Fasching, Bo Gao, Yi Lu, Jonathan Beesley, Siddhartha Kar, Jonathan P. Tyrer, and Sharon E. Johnatty
Abstract: Supplementary Figures 1-5, Tables 1-8. Supplementary Figure 1: Overview of the analytic approach. Supplementary Figure 2: QQ plots of SNPs with MAF â‰¥0.02 and imputation r2 â‰¥0.9 associated with Overall Survival in A. Supplementary Figure 3: â€˜All OCACâ€™ histology-adjusted analysis. Supplementary Figure 4: Forest plots of promising SNPs. Supplementary Figure 5: KM-Plotter graphs of significant associations with outcome. Supplementary Table 1: All studies (OCAC & TCGA) eligible for analyses according to first-line chemotherapy. Supplementary Table 2: Description of individual OCAC studies included in the secondary 'all OCAC' analysis. Supplementary Table 3a: Overall Survival estimates for selected SNPs (MAF â‰¥0.02) comparing iCOGS imputed (r2 â‰¥0.3) and iPLEX genotyped samples. Supplementary Table 3b: Progression-free Survival estimates for selected SNPs (MAF â‰¥0.02) comparing iCOGS imputed (r2 â‰¥0.3) and iPLEX genotyped samples. Supplementary Table 4: SNPs with imputation r2 â‰¥0.9, EAF â‰¥0.02 and p â‰¤ 1E-05 for at least one of four outcomes analyzed in cases selected according to first-line chemotherapy. Supplementary Table 5: Meta-analysis of largest possible sample (TCGA, non-overlapping iCOGS and iplex genotyped) for selected promising SNPs analyzed in cases selected according to first-line chemotherapy. Supplementary Table 6: Significant association between protein-coding genes within 1Mb of promising SNPs and ovarian cancer outcomes. Supplementary Table 7: SNPs with imputation r-sqâ‰¥0.9 and p â‰¤ 1E-05 for Overall Survival in histology-adj 'all OCAC' analysis. Supplementary Table 8: iCOGS estimates for SNPs previously identified to be associated with response to chemotherapy as reported in the aNHGRI GWAS catalog.
Published: 2023

46. Supplementary Table 2 from Gene Set Analysis of Survival Following Ovarian Cancer Implicates Macrolide Binding and Intracellular Signaling Genes

Author: Ellen L. Goode, Thomas A. Sellers, Paul D.P. Pharoah, Lynn C. Hartmann, Simon A. Gayther, Rebecca Sutphen, Joellen Schildkraut, Aleksandra Gentry-Maharaj, Usha Menon, Ed Iversen, Y. Ann Chen, Zhihua Chen, Robert A. Vierkant, Julie M. Cunningham, Susan J. Ramus, Jonathan Tyrer, David Fenstermacher, Kelly L. Bolton, Honglin Song, Ya-Yu Tsai, Gregory D. Jenkins, and Brooke L. Fridley
Abstract: PDF file - 130K
Published: 2023

47. Data from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author: Ellen L. Goode, Thomas A. Sellers, Brooke L. Fridley, Paul D.P. Pharoah, Catherine M. Phelan, Jennifer Permuth-Wey, Joellen M. Schildkraut, Andrew Berchuck, Argyrios Ziogas, Hannah Yang, Anna H. Wu, Lynne R. Wilkens, Christine Walsh, Allison F. Vitonis, Robert A. Vierkant, David J. van den Berg, Jonathan P. Tyrer, Pamela J. Thompson, Kathryn L. Terry, Honglin Song, Susan J. Ramus, Malcolm C. Pike, Irene Orlow, Kirsten B. Moysich, Francesmary Modugno, Janusz Menkiszak, Jan Lubinski, Jolanta Lissowska, Hui-Yi Lin, Jenny Lester, Sharon E. Johnatty, Allan Jensen, Edwin S. Iversen, Martin Gore, Aleksandra Gentry-Maharaj, Simon A. Gayther, Robert P. Edwards, Ed M. Dicks, Anna deFazio, Cezary Cybulski, Julie M. Cunningham, Michael E. Carney, Louise A. Brinton, Maria Bisogna, Yukie T. Bean, Nicolas Wentzensen, Mary Anne Rossing, Tanja Pejovic, Celeste L. Pearce, Roberta B. Ness, Usha Menon, Douglas A. Levine, Susanne K. Kjaer, Beth Y. Karlan, Jacek Gronwald, Marc T. Goodman, Jennifer A. Doherty, Daniel Cramer, Elisa V. Bandera, Hoda Anton-Culver, Madalene A. Earp, Zachary C. Fogarty, Melissa C. Larson, Yian Ann Chen, Ailith Pirie, and Stacey J. Winham
Abstract: Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).Methods: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped).Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E−6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E−6; Pcorrected = 0.01).Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.Impact: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446–54. ©2016 AACR.
Published: 2023

48. Data from Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium

Author: Ellen L. Goode, Thomas A. Sellers, Joellen M. Schildkraut, Anna H. Wu, Lynne R. Wilkens, Alice S. Whittemore, Shan Wang-Gohrke, Robert A. Vierkant, David Van Den Berg, Shelley S. Tworoger, Daniel O. Stram, Honglin Song, Susan J. Ramus, Paul D.P. Pharoah, Celeste L. Pearce, Rachel T. Palmieri, Roberta B. Ness, Kirsten Moysich, Patricia G. Moorman, Usha Menon, Galina Lurie, Susanne Krüger Kjær, Estrid Høgdall, Aleksandra Gentry-Maharaj, Simon A. Gayther, Margaret A. Gates, Brooke L. Fridley, Zachary S. Fredericksen, Douglas F. Easton, Jennifer A. Doherty, Richard A. DiCioccio, Julie M. Cunningham, Daniel W. Cramer, Georgia Chenevix-Trench, Jenny Chang-Claude, Michael E. Carney, Sony Brar, Andrew Berchuck, Jonathan Beesley, Hoda Anton-Culver, Martin Köbel, Penelope M. Webb, Mary Anne Rossing, Valerie McGuire, Marc T. Goodman, and Linda E. Kelemen
Abstract: Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type.Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site.Results: The five polymorphisms were not associated with ovarian carcinoma overall (Ptrend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; Pheterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification.Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology. Cancer Epidemiol Biomarkers Prev; 19(7); 1822–30. ©2010 AACR.
Published: 2023

49. Supplemental Figure 1 from Assessment of Multifactor Gene–Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors

Author: Brooke L. Fridley, Ellen L. Goode, Paul Pharoah, Joellen M. Schildkraut, Celeste Leigh Pearce, Hannah Yang, Anna H. Wu, Lynne R. Wilkens, Alice S. Whittemore, Nicolas Wentzensen, Shan Wang-Gohrke, Robert A. Vierkant, David J. van den Berg, Pamela J. Thompson, Honglin Song, Joseph Rothstein, Mary Anne Rossing, Susan J. Ramus, Malcolm C. Pike, Roberta B. Ness, Kirsten B. Moysich, Francesmary Modugno, Usha Menon, Leon Massuger, Galina Lurie, Melissa C. Larson, Susanne K. Kjaer, Lambertus A. Kiemeney, Sharon E. Johnatty, Allan Jensen, Estrid Høgdall, Marc T. Goodman, Aleksandra Gentry-Maharaj, Simon A. Gayther, Robert P. Edwards, Jennifer A. Doherty, Anna DeFazio, Julie M. Cunningham, Louise Brinton, Andrew Berchuck, Hoda Anton-Culver, Anja Rudolph, Jenny Chang-Claude, Penelope Webb, Weiva Sieh, Valerie McGuire, Jonathan P. Tyrer, Rama Raghavan, and Joseph L. Usset
Abstract: Potential hormonal mechanism to motivate investigation of multi-factor obesity-hormone related risk factors - SNP interactions.
Published: 2023

50. Data from Assessment of Multifactor Gene–Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors

Author: Brooke L. Fridley, Ellen L. Goode, Paul Pharoah, Joellen M. Schildkraut, Celeste Leigh Pearce, Hannah Yang, Anna H. Wu, Lynne R. Wilkens, Alice S. Whittemore, Nicolas Wentzensen, Shan Wang-Gohrke, Robert A. Vierkant, David J. van den Berg, Pamela J. Thompson, Honglin Song, Joseph Rothstein, Mary Anne Rossing, Susan J. Ramus, Malcolm C. Pike, Roberta B. Ness, Kirsten B. Moysich, Francesmary Modugno, Usha Menon, Leon Massuger, Galina Lurie, Melissa C. Larson, Susanne K. Kjaer, Lambertus A. Kiemeney, Sharon E. Johnatty, Allan Jensen, Estrid Høgdall, Marc T. Goodman, Aleksandra Gentry-Maharaj, Simon A. Gayther, Robert P. Edwards, Jennifer A. Doherty, Anna DeFazio, Julie M. Cunningham, Louise Brinton, Andrew Berchuck, Hoda Anton-Culver, Anja Rudolph, Jenny Chang-Claude, Penelope Webb, Weiva Sieh, Valerie McGuire, Jonathan P. Tyrer, Rama Raghavan, and Joseph L. Usset
Abstract: Background: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene–environment interactions related to hormone-related risk factors could differ between obese and non-obese women.Methods: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case–control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed.Results: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10−6) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10−5). The most notable obesity–gene–hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10−6).Conclusions: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2. Future work is needed to develop powerful statistical methods able to detect these complex interactions.Impact: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780–90. ©2016 AACR.
Published: 2023

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