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1,434 results on '"Kaufmann, Scott H."'

1. Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium

Author

Meagher, Nicola S, White, Kami K, Wilkens, Lynne R, Bandera, Elisa V, Berchuck, Andrew, Carney, Michael E, Cramer, Daniel W, Cushing-Haugen, Kara L, Jordan, Susan, Kaufmann, Scott H, Le, Nhu D, Pike, Malcolm C, Riggan, Marjorie, Qin, Bo, Rothstein, Joseph H, Titus, Linda, Winham, Stacey J, Anton-Culver, Hoda, Doherty, Jennifer A, Goode, Ellen L, Pearce, Celeste Leigh, Risch, Harvey A, Webb, Penelope M, Cook, Linda S, Goodman, Marc T, Harris, Holly R, Le Marchand, Loic, McGuire, Valerie, Pharoah, Paul DP, Sarink, Danja, Schildkraut, Joellen M, Sieh, Weiva, Terry, Kathryn L, Thompson, Pamela J, Whittemore, Alice S, Wu, Anna H, Peres, Lauren C, and Merritt, Melissa A

Subjects
Epidemiology, Health Sciences, Prevention, Women's Health, Minority Health, Rare Diseases, Ovarian Cancer, Cancer, Adult, Aged, Female, Humans, Middle Aged, Asian, Carcinoma, Ovarian Epithelial, Case-Control Studies, Contraceptives, Oral, Ethnicity, Hispanic or Latino, Logistic Models, Native Hawaiian or Other Pacific Islander, Odds Ratio, Ovarian Neoplasms, Parity, Risk Factors, Smoking, Sterilization, Tubal, United States, White, ovarian cancer, risk factors, race, ethnicity, Mathematical Sciences, Medical and Health Sciences
Abstract

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.

Published
2024

2. Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma

Author

Saner, Flurina AM, Takahashi, Kazuaki, Budden, Timothy, Pandey, Ahwan, Ariyaratne, Dinuka, Zwimpfer, Tibor A, Meagher, Nicola S, Fereday, Sian, Twomey, Laura, Pishas, Kathleen I, Hoang, Therese, Bolithon, Adelyn, Traficante, Nadia, Group, for the Australian Ovarian Cancer Study, Alsop, Kathryn, Christie, Elizabeth L, Kang, Eun-Young, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Alsop, Jennifer, Beckmann, Matthias W, Boros, Jessica, Brand, Alison H, Brooks-Wilson, Angela, Carney, Michael E, Coulson, Penny, Courtney-Brooks, Madeleine, Cushing-Haugen, Kara L, Cybulski, Cezary, El-Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Gilks, C Blake, Harnett, Paul R, Harris, Holly R, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Jakubowska, Anna, Jimenez-Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Kluz, Tomasz, Koziak, Jennifer M, Kristjansdottir, Björg, Le, Nhu D, Lener, Marcin, Lester, Jenny, Lubiński, Jan, Mateoiu, Constantina, Orsulic, Sandra, Ruebner, Matthias, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Sherman, Mark E, Shvetsov, Yurii B, Soong, T Rinda, Steed, Helen, Sukumvanich, Paniti, Talhouk, Aline, Taylor, Sarah E, Vierkant, Robert A, Wang, Chen, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Anglesio, Michael S, Berchuck, Andrew, Brenton, James D, Campbell, Ian, Cook, Linda S, Doherty, Jennifer A, Fasching, Peter A, Fortner, Renée T, Goodman, Marc T, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kelemen, Linda E, Menon, Usha, Modugno, Francesmary, Pharoah, Paul DP, Schildkraut, Joellen M, Sundfeldt, Karin, Swerdlow, Anthony J, Goode, Ellen L, DeFazio, Anna, Köbel, Martin, Ramus, Susan J, Bowtell, David DL, and Garsed, Dale W

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Orphan Drug, Human Genome, Rare Diseases, Cancer, Genetics, Women's Health, Cancer Genomics, Ovarian Cancer, Precision Medicine, 2.1 Biological and endogenous factors, Humans, Female, Ovarian Neoplasms, BRCA2 Protein, BRCA1 Protein, Cystadenocarcinoma, Serous, Retinoblastoma Binding Proteins, Prognosis, Ubiquitin-Protein Ligases, Neoplasm Grading, Lymphocytes, Tumor-Infiltrating, Middle Aged, Germ-Line Mutation, Gene Expression Regulation, Neoplastic, Aged, Biomarkers, Tumor, CD8-Positive T-Lymphocytes, Australian Ovarian Cancer Study Group, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Published
2024

3. Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors

Author

Venkatachalam, Annapoorna, Correia, Cristina, Peterson, Kevin L., Hou, Xianon, Schneider, Paula A., Strathman, Annabella R., Flatten, Karen S., Sine, Chance C., Balczewski, Emily A., McGehee, Cordelia D., Larson, Melissa C., Duffield, Laura N., Meng, X. Wei, Vincelette, Nicole D., Ding, Husheng, Oberg, Ann L., Couch, Fergus J., Swisher, Elizabeth M., Li, Hu, Weroha, S. John, and Kaufmann, Scott H.

Published
2024
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4. AMPK inhibition sensitizes acute leukemia cells to BH3 mimetic-induced cell death

Author

Jia, Jia, Ji, Wenbo, Saliba, Antoine N., Csizmar, Clifford M., Ye, Kaiqin, Hu, Lei, Peterson, Kevin L., Schneider, Paula A., Meng, X. Wei, Venkatachalam, Annapoorna, Patnaik, Mrinal M., Webster, Jonathan A., Smith, B. Douglas, Ghiaur, Gabriel, Wu, Xinyan, Zhong, Jun, Pandey, Akhilesh, Flatten, Karen S., Deng, Qingmei, Wang, Hongzhi, Kaufmann, Scott H., and Dai, Haiming

Published
2024
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5. Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort

Author

Emiloju, Oluwadunni E., Yin, Jun, Koubek, Emily, Reid, Joel M., Borad, Mitesh J., Lou, Yanyan, Seetharam, Mahesh, Edelman, Martin J., Sausville, Edward A., Jiang, Yixing, Kaseb, Ahmed O., Posey, James A., Davis, Sarah L., Gores, Gregory J., Roberts, Lewis R., Takebe, Naoko, Schwartz, Gary K., Hendrickson, Andrea E. Wahner, Kaufmann, Scott H., Adjei, Alex A., Hubbard, Joleen M., and Costello, Brian A.

Published
2024
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6. CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Author

Kang, Eun‐Young, Weir, Ashley, Meagher, Nicola S, Farrington, Kyo, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng‐Han, Riggan, Marjorie J, Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S, Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Brucker, Sara Y, Carney, Michael E, Casablanca, Yovanni, Cazorla‐Jiménez, Alicia, Cohen, Paul A, Conrads, Thomas P, Cook, Linda S, Coulson, Penny, Courtney‐Brooks, Madeleine, Cramer, Daniel W, Crowe, Philip, Cunningham, Julie M, Cybulski, Cezary, Darcy, Kathleen M, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J, Gayther, Simon A, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Group, AOCS, Grube, Marcel, Harnett, Paul R, Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L, Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y, Polo, Susanna Hernando, Heublein, Sabine, Hirasawa, Akira, Høgdall, Estrid, Høgdall, Claus K, Horlings, Hugo M, Huntsman, David G, Huzarski, Tomasz, Jewell, Andrea, Jimenez‐Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Khabele, Dineo, Kommoss, Felix KF, Kruitwagen, Roy FPM, Lambrechts, Diether, Le, Nhu D, Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubiński, Jan, Madan, Rashna, Maxwell, G Larry, Modugno, Francesmary, Neuhausen, Susan L, Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, José, Pearce, Celeste Leigh, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rodríguez‐Antona, Cristina, Ruebner, Matthias, and Ryan, Andy

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Women's Health, Orphan Drug, Rare Diseases, Clinical Research, Ovarian Cancer, Cancer, 2.1 Biological and endogenous factors, Female, Humans, Ovarian Neoplasms, Transcription Factors, Carcinoma, RNA, Messenger, Cystadenocarcinoma, Serous, Oncogene Proteins, Cyclin E, CCNE1 amplification, cyclin E1 expression, high-grade serous carcinoma, ovarian cancer, prognosis, AOCS Group, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Public health
Abstract

BackgroundCyclin 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.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-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.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

Published
2023

8. Apoptotic stress causes mtDNA release during senescence and drives the SASP

Author

Victorelli, Stella, Salmonowicz, Hanna, Chapman, James, Martini, Helene, Vizioli, Maria Grazia, Riley, Joel S., Cloix, Catherine, Hall-Younger, Ella, Machado Espindola-Netto, Jair, Jurk, Diana, Lagnado, Anthony B., Sales Gomez, Lilian, Farr, Joshua N., Saul, Dominik, Reed, Rebecca, Kelly, George, Eppard, Madeline, Greaves, Laura C., Dou, Zhixun, Pirius, Nicholas, Szczepanowska, Karolina, Porritt, Rebecca A., Huang, Huijie, Huang, Timothy Y., Mann, Derek A., Masuda, Claudio Akio, Khosla, Sundeep, Dai, Haiming, Kaufmann, Scott H., Zacharioudakis, Emmanouil, Gavathiotis, Evripidis, LeBrasseur, Nathan K., Lei, Xue, Sainz, Alva G., Korolchuk, Viktor I., Adams, Peter D., Shadel, Gerald S., Tait, Stephen W. G., and Passos, João F.

Published
2023
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9. DAGBagM: learning directed acyclic graphs of mixed variables with an application to identify protein biomarkers for treatment response in ovarian cancer

Author

Chowdhury, Shrabanti, Wang, Ru, Yu, Qing, Huntoon, Catherine J, Karnitz, Larry M, Kaufmann, Scott H, Gygi, Steven P, Birrer, Michael J, Paulovich, Amanda G, Peng, Jie, and Wang, Pei

Subjects
Information and Computing Sciences, Machine Learning, Rare Diseases, Cancer, Ovarian Cancer, Good Health and Well Being, Biomarkers, Causality, Child, Computer Simulation, Confounding Factors, Epidemiologic, Female, Humans, Ovarian Neoplasms, Proteomics, Sensitive and resistant/refractory, Hill climbing, Bootstrap aggregation, Mathematical Sciences, Biological Sciences, Bioinformatics, Biological sciences, Information and computing sciences, Mathematical sciences
Abstract

BackgroundApplying directed acyclic graph (DAG) models to proteogenomic data has been shown effective for detecting causal biomarkers of complex diseases. However, there remain unsolved challenges in DAG learning to jointly model binary clinical outcome variables and continuous biomarker measurements.ResultsIn this paper, we propose a new tool, DAGBagM, to learn DAGs with both continuous and binary nodes. By using appropriate models, DAGBagM allows for either continuous or binary nodes to be parent or child nodes. It employs a bootstrap aggregating strategy to reduce false positives in edge inference. At the same time, the aggregation procedure provides a flexible framework to robustly incorporate prior information on edges.ConclusionsThrough extensive simulation experiments, we demonstrate that DAGBagM has superior performance compared to alternative strategies for modeling mixed types of nodes. In addition, DAGBagM is computationally more efficient than two competing methods. When applying DAGBagM to proteogenomic datasets from ovarian cancer studies, we identify potential protein biomarkers for platinum refractory/resistant response in ovarian cancer. DAGBagM is made available as a github repository at https://github.com/jie108/dagbagM .

Published
2022

11. Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer

Author

Jayaraman, Swaathi, Wu, Xinyan, Kalari, Krishna R., Tang, Xiaojia, Kuffel, Mary J., Bruinsma, Elizabeth S., Jalali, Shahrzad, Peterson, Kevin L., Correia, Cristina, Kudgus, Rachel A., Kaufmann, Scott H., Renuse, Santosh, Ingle, James N., Reid, Joel M., Ames, Matthew M., Fields, Alan P., Schellenberg, Matthew J., Hawse, John R., Pandey, Akhilesh, and Goetz, Matthew P.

Published
2023
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14. PARP inhibitor maintenance for primary ovarian cancer – A missed opportunity for precision medicine

Author

Wethington, Stephanie L, Wahner-Hendrickson, Andrea E, Swisher, Elizabeth M, Kaufmann, Scott H, Karlan, Beth Y, Fader, Amanda Nickles, and Dowdy, Sean C

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, BRCA1 Protein, BRCA2 Protein, DNA Repair-Deficiency Disorders, Female, Humans, Mutation, Ovarian Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Precision Medicine, Randomized Controlled Trials as Topic, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis, Reproductive medicine
Published
2021

15. Homologous recombination—deficient mutation cluster in tumor suppressor RAD51C identified by comprehensive analysis of cancer variants

Author

Prakash, Rohit, Rawal, Yashpal, Sullivan, Meghan R., Grundy, McKenzie K., Bret, Hélène, Mihalevic, Michael J., Rein, Hayley L., Baird, Jared M., Darrah, Kristie, Zhang, Fang, Wang, Raymond, Traina, Tiffany A., Radke, Marc R., Kaufmann, Scott H., Swisher, Elizabeth M., Guérois, Raphaël, Modesti, Mauro, Sung, Patrick, Jasin, Maria, and Bernstein, Kara A.

Published
2022

16. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).

Author

Swisher, Elizabeth M, Kwan, Tanya T, Oza, Amit M, Tinker, Anna V, Ray-Coquard, Isabelle, Oaknin, Ana, Coleman, Robert L, Aghajanian, Carol, Konecny, Gottfried E, O'Malley, David M, Leary, Alexandra, Provencher, Diane, Welch, Stephen, Chen, Lee-May, Wahner Hendrickson, Andrea E, Ma, Ling, Ghatage, Prafull, Kristeleit, Rebecca S, Dorigo, Oliver, Musafer, Ashan, Kaufmann, Scott H, Elvin, Julia A, Lin, Douglas I, Chambers, Setsuko K, Dominy, Erin, Vo, Lan-Thanh, Goble, Sandra, Maloney, Lara, Giordano, Heidi, Harding, Thomas, Dobrovic, Alexander, Scott, Clare L, Lin, Kevin K, and McNeish, Iain A

Subjects
Humans, Ovarian Neoplasms, Neoplasm Recurrence, Local, Platinum, Indoles, DNA-Binding Proteins, BRCA1 Protein, BRCA2 Protein, Antineoplastic Agents, DNA Methylation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Promoter Regions, Genetic, Poly(ADP-ribose) Polymerase Inhibitors, Carcinoma, Ovarian Epithelial
Abstract

ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity.

Published
2021

19. Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

Author

Chowdhury, Shrabanti, Kennedy, Jacob J., Ivey, Richard G., Murillo, Oscar D., Hosseini, Noshad, Song, Xiaoyu, Petralia, Francesca, Calinawan, Anna, Savage, Sara R., Berry, Anna B., Reva, Boris, Ozbek, Umut, Krek, Azra, Ma, Weiping, da Veiga Leprevost, Felipe, Ji, Jiayi, Yoo, Seungyeul, Lin, Chenwei, Voytovich, Uliana J., Huang, Yajue, Lee, Sun-Hee, Bergan, Lindsay, Lorentzen, Travis D., Mesri, Mehdi, Rodriguez, Henry, Hoofnagle, Andrew N., Herbert, Zachary T., Nesvizhskii, Alexey I., Zhang, Bing, Whiteaker, Jeffrey R., Fenyo, David, McKerrow, Wilson, Wang, Joshua, Schürer, Stephan C., Stathias, Vasileios, Chen, X. Steven, Barcellos-Hoff, Mary Helen, Starr, Timothy K., Winterhoff, Boris J., Nelson, Andrew C., Mok, Samuel C., Kaufmann, Scott H., Drescher, Charles, Cieslik, Marcin, Wang, Pei, Birrer, Michael J., and Paulovich, Amanda G.

Published
2023
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20. Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE)

Author

Talhouk, Aline, George, Joshy, Wang, Chen, Budden, Timothy, Tan, Tuan Zea, Chiu, Derek S, Kommoss, Stefan, San Leong, Huei, Chen, Stephanie, Intermaggio, Maria P, Gilks, Blake, Nazeran, Tayyebeh M, Volchek, Mila, Elatre, Wafaa, Bentley, Rex C, Senz, Janine, Lum, Amy, Chow, Veronica, Sudderuddin, Hanwei, Mackenzie, Robertson, Leong, Samuel CY, Liu, Geyi, Johnson, Dustin, Chen, Billy, Group, AOCS, Alsop, Jennifer, Banerjee, Susana N, Behrens, Sabine, Bodelon, Clara, Brand, Alison H, Brinton, Louise, Carney, Michael E, Chiew, Yoke-Eng, Cushing-Haugen, Kara L, Cybulski, Cezary, Ennis, Darren, Fereday, Sian, Fortner, Renée T, García-Donas, Jesús, Gentry-Maharaj, Aleksandra, Glasspool, Rosalind, Goranova, Teodora, Greene, Casey S, Haluska, Paul, Harris, Holly R, Hendley, Joy, Hernandez, Brenda Y, Herpel, Esther, Jimenez-Linan, Mercedes, Karpinskyj, Chloe, Kaufmann, Scott H, Keeney, Gary L, Kennedy, Catherine J, Köbel, Martin, Koziak, Jennifer M, Larson, Melissa C, Lester, Jenny, Lewsley, Liz-Anne, Lissowska, Jolanta, Lubiński, Jan, Luk, Hugh, Macintyre, Geoff, Mahner, Sven, McNeish, Iain A, Menkiszak, Janusz, Nevins, Nikilyn, Osorio, Ana, Oszurek, Oleg, Palacios, José, Hinsley, Samantha, Pearce, Celeste L, Pike, Malcolm C, Piskorz, Anna M, Ray-Coquard, Isabelle, Rhenius, Valerie, Rodriguez-Antona, Cristina, Sharma, Raghwa, Sherman, Mark E, De Silva, Dilrini, Singh, Naveena, Sinn, Peter, Slamon, Dennis, Song, Honglin, Steed, Helen, Stronach, Euan A, Thompson, Pamela J, Tołoczko, Aleksandra, Trabert, Britton, Traficante, Nadia, Tseng, Chiu-Chen, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Winterhoff, Boris, Beeghly-Fadiel, Alicia, Benitez, Javier, Berchuck, Andrew, Brenton, James D, Brown, Robert, and Chang-Claude, Jenny

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer Genomics, Orphan Drug, Genetics, Precision Medicine, Rare Diseases, Human Genome, Women's Health, Ovarian Cancer, Cancer, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Aged, Algorithms, Cystadenoma, Serous, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphocytes, Tumor-Infiltrating, Middle Aged, Neoplasm Grading, Neoplasm Proteins, Neoplasm, Residual, Ovarian Neoplasms, Transcriptome, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeGene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.Experimental designAdopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.ResultsGene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations.ConclusionsWe validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.

Published
2020

21. Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.

Author

Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N, Chow, Christine, Nazeran, Tayyebeh M, Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D, Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y, McCauley, Bryan M, Karpinskyj, Chloe, de Sousa, Christiani B, Høgdall, Claus, Tiezzi, Daniel G, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M, Lester, Jenny, Rothstein, Joseph H, de Andrade, Jurandyr M, Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R, Garcia, Maria J, Intermaggio, Maria P, Alcaraz, Marie-Lyne, Brett, Mary A, Beckmann, Matthias W, Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E, Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B, Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y, Kaufmann, Scott H, Fereday, Sian, Gayther, Simon, Winham, Stacey J, Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A, McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B, Whittemore, Alice S, Staebler, Annette, Karlan, Beth Y, Rodriguez-Antona, Cristina, Bowtell, David D, Goode, Ellen L, Høgdall, Estrid, Candido Dos Reis, Francisco J, Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, Fasching, Peter A, Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G, Köbel, Martin, Ramus, Susan J, Pharoah, Paul DP, and Brenton, James D

Subjects
Oncology & Carcinogenesis, Oncology and Carcinogenesis, Public Health and Health Services
Abstract

BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value

Published
2020

23. Author Correction: Apoptotic stress causes mtDNA release during senescence and drives the SASP

Author

Victorelli, Stella, Salmonowicz, Hanna, Chapman, James, Martini, Helene, Vizioli, Maria Grazia, Riley, Joel S., Cloix, Catherine, Hall-Younger, Ella, Machado Espindola-Netto, Jair, Jurk, Diana, Lagnado, Anthony B., Sales Gomez, Lilian, Farr, Joshua N., Saul, Dominik, Reed, Rebecca, Kelly, George, Eppard, Madeline, Greaves, Laura C., Dou, Zhixun, Pirius, Nicholas, Szczepanowska, Karolina, Porritt, Rebecca A., Huang, Huijie, Huang, Timothy Y., Mann, Derek A., Masuda, Claudio Akio, Khosla, Sundeep, Dai, Haiming, Kaufmann, Scott H., Zacharioudakis, Emmanouil, Gavathiotis, Evripidis, LeBrasseur, Nathan K., Lei, Xue, Sainz, Alva G., Korolchuk, Viktor I., Adams, Peter D., Shadel, Gerald S., Tait, Stephen W. G., and Passos, João F.

Published
2024
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24. Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women

Author

Grant, Delores J, Manichaikul, Ani, Alberg, Anthony J, Bandera, Elisa V, Barnholtz‐Sloan, Jill, Bondy, Melissa, Cote, Michele L, Funkhouser, Ellen, Moorman, Patricia G, Peres, Lauren C, Peters, Edward S, Schwartz, Ann G, Terry, Paul D, Wang, Xin‐Qun, Keku, Temitope O, Hoyo, Cathrine, Berchuck, Andrew, Sandler, Dale P, Taylor, Jack A, O’Brien, Katie M, Edwards, Digna R Velez, Edwards, Todd L, Beeghly‐Fadiel, Alicia, Wentzensen, Nicolas, Pearce, Celeste Leigh, Wu, Anna H, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Rothstein, Joseph H, Modugno, Francesmary, Ness, Roberta, Moysich, Kirsten, Rossing, Mary Anne, Doherty, Jennifer A, Sellers, Thomas A, Permuth‐Way, Jennifer B, Monteiro, Alvaro N, Levine, Douglas A, Setiawan, Veronica Wendy, Haiman, Christopher A, LeMarchand, Loic, Wilkens, Lynne R, Karlan, Beth Y, Menon, Usha, Ramus, Susan, Gayther, Simon, Gentry‐Maharaj, Aleksandra, Terry, Kathryn L, Cramer, Daniel W, Goode, Ellen L, Larson, Melissa C, Kaufmann, Scott H, Cannioto, Rikki, Odunsi, Kunle, Etter, John L, Huang, Ruea‐Yea, Bernardini, Marcus Q, Tone, Alicia A, May, Taymaa, Goodman, Marc T, Thompson, Pamela J, Carney, Michael E, Tworoger, Shelley S, Poole, Elizabeth M, Lambrechts, Diether, Vergote, Ignace, Vanderstichele, Adriaan, Van Nieuwenhuysen, Els, Anton‐Culver, Hoda, Ziogas, Argyrios, Brenton, James D, Bjorge, Line, Salvensen, Helga B, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bruegl, Amanda, Moffitt, Melissa, Cook, Linda, Le, Nhu D, Brooks‐Wilson, Angela, Kelemen, Linda E, Pharoah, Paul DP, Song, Honglin, Campbell, Ian, Eccles, Diana, DeFazio, Anna, Kennedy, Catherine J, and Schildkraut, Joellen M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Biotechnology, Ovarian Cancer, Women's Health, Genetics, Nutrition, Rare Diseases, Human Genome, Cancer, 2.1 Biological and endogenous factors, Black or African American, Bayes Theorem, Carcinoma, Ovarian Epithelial, ErbB Receptors, Female, Genetic Association Studies, Glucuronosyltransferase, Humans, Logistic Models, Middle Aged, Neoplasm Grading, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Receptors, Calcitriol, Vitamin D, African ancestry risk, genetic association, ovarian cancer, vitamin D pathway, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

Published
2019

25. A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer

Author

Manzo, Julia, Puhalla, Shannon, Pahuja, Shalu, Ding, Fei, Lin, Yan, Appleman, Leonard, Tawbi, Hussein, Stoller, Ronald, Lee, James J., Diergaarde, Brenda, Kiesel, Brian F., Yu, Jing, Tan, Antoinette R., Belani, Chandra P., Chew, Helen, Garcia, Agustin A., Morgan, Robert J., Wahner Hendrickson, Andrea E., Visscher, Daniel W., Hurley, Rachel M., Kaufmann, Scott H., Swisher, Elizabeth M., Oesterreich, Steffi, Katz, Tiffany, Ji, Jiuping, Zhang, Yiping, Parchment, Ralph E., Chen, Alice, Duan, Wenrui, Giranda, Vincent, Shepherd, Stacie P., Ivy, S. Percy, Chu, Edward, and Beumer, Jan H.

Published
2022
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27. Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study

Author

Swisher, Elizabeth M., Aghajanian, Carol, O'Malley, David M., Fleming, Gini F., Kaufmann, Scott H., Levine, Douglas A., Birrer, Michael J., Moore, Kathleen N., Spirtos, Nick M., Shahin, Mark S., Reid, Thomas J., Friedlander, Michael, Steffensen, Karina Dahl, Okamoto, Aikou, Sehgal, Vasudha, Ansell, Peter J., Dinh, Minh H., Bookman, Michael A., and Coleman, Robert L.

Published
2022
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29. Lestaurtinib′s antineoplastic activity converges on JAK/STAT signaling to inhibit advanced forms of therapy resistant ovarian cancer

Author

Rodman, Esther P B, primary, Emch, Michael J, additional, Hou, Xiaonan, additional, Bajaj, Archit, additional, Pearson, Nicole A, additional, John, August, additional, Ortiz, Yamillie, additional, Bass, Adam D, additional, Baldassarre, Gustavo, additional, Kaufmann, Scott H, additional, Weroha, Saravut John, additional, and Hawse, John R, additional

Published
2024
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30. Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC-Alarmin Axis

Author

Vincelette, Nicole D., primary, Yu, Xiaoqing, additional, Kuykendall, Andrew T., additional, Moon, Jungwon, additional, Su, Siyuan, additional, Cheng, Chia-Ho, additional, Sammut, Rinzine, additional, Razabdouski, Tiffany N., additional, Nguyen, Hai Vu, additional, Eksioglu, Erika A., additional, Chan, Onyee, additional, Al Ali, Najla, additional, Patel, Parth C., additional, Lee, Dae Hyun, additional, Nakanishi, Shima, additional, Ferreira, Renan B., additional, Hyjek, Elizabeth, additional, Mo, Qianxing, additional, Cory, Suzanne, additional, Lawrence, Harshani R., additional, Zhang, Ling, additional, Murphy, Daniel J., additional, Komrokji, Rami S., additional, Lee, Daesung, additional, Kaufmann, Scott H., additional, Cleveland, John L., additional, and Yun, Seongseok, additional

Published
2024
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31. Characterization of patients with long-term responses to rucaparib treatment in recurrent ovarian cancer

Author

Swisher, Elizabeth M., Kristeleit, Rebecca S., Oza, Amit M., Tinker, Anna V., Ray-Coquard, Isabelle, Oaknin, Ana, Coleman, Robert L., Burris, Howard A., Aghajanian, Carol, O'Malley, David M., Leary, Alexandra, Welch, Stephen, Provencher, Diane, Shapiro, Geoffrey I., Chen, Lee-may, Shapira-Frommer, Ronnie, Kaufmann, Scott H., Goble, Sandra, Maloney, Lara, Kwan, Tanya, Lin, Kevin K., and McNeish, Iain A.

Published
2021
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33. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses

Author

Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Au-Yeung, George, Böhm, Maret, Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mileshkin, Linda, Pyman, Jan, Samimi, Goli, Sharma, Ragwha, and Campbell, Ian G.

Published
2021
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34. List of contributors

Author

Chung, Michael C., primary, Dai, Haiming, additional, Guan, Juan, additional, Jia, Jia, additional, Kang, Rui, additional, Kaufmann, Scott H., additional, Law, Mary E., additional, Law, Brian K., additional, Liao, Daiqing, additional, Meng, X. Wei, additional, Sethi, Gautam, additional, Shanmugam, Muthu K., additional, Shu, Xiaokun, additional, Tang, Daolin, additional, To, Tsz-Leung, additional, Wang, Mengxiong, additional, and Ye, Kaiqin, additional

Published
2022
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36. Therapeutic options for mucinous ovarian carcinoma

Author

Gorringe, Kylie L., Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Amarasinghe, Kaushalya C., Ananda, Sumitra, Bowtell, David D.L., Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Fereday, Sian, Gilks, C. Blake, Gourley, Charlie, Hadley, Alison M., Hendley, Joy, Hunter, Sally M., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, Li, Jason, Lupat, Richard, McNally, Orla M., McAlpine, Jessica N., Pyman, Jan, Rowley, Simone M., Salazar, Carolina, Saunders, Hugo, Semple, Timothy, Stephens, Andrew N., Thio, Niko, Torres, Michelle C., Traficante, Nadia, Zethoven, Magnus, Antill, Yoland C., Campbell, Ian G., and Scott, Clare L.

Published
2020
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37. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial

Author

Swisher, Elizabeth M, Lin, Kevin K, Oza, Amit M, Scott, Clare L, Giordano, Heidi, Sun, James, Konecny, Gottfried E, Coleman, Robert L, Tinker, Anna V, O'Malley, David M, Kristeleit, Rebecca S, Ma, Ling, Bell-McGuinn, Katherine M, Brenton, James D, Cragun, Janiel M, Oaknin, Ana, Ray-Coquard, Isabelle, Harrell, Maria I, Mann, Elaina, Kaufmann, Scott H, Floquet, Anne, Leary, Alexandra, Harding, Thomas C, Goble, Sandra, Maloney, Lara, Isaacson, Jeff, Allen, Andrew R, Rolfe, Lindsey, Yelensky, Roman, Raponi, Mitch, and McNeish, Iain A

Subjects
Rare Diseases, Genetics, Cancer, Ovarian Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Aged, Antineoplastic Agents, BRCA1 Protein, BRCA2 Protein, Carcinoma, Ovarian Epithelial, Drug Resistance, Neoplasm, Fallopian Tube Neoplasms, Female, Follow-Up Studies, Germ-Line Mutation, Humans, Indoles, International Agencies, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Peritoneal Neoplasms, Platinum, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases, Prognosis, Prospective Studies, Salvage Therapy, Survival Rate, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPoly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.MethodsARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing.Findings256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8-10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup, 5·7 months (5·3-7·6) in the LOH high subgroup, and 5·2 months (3·6-5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p

Published
2017

38. Abstract B098: Impact of dexamethasone on chemotherapy response in ovarian cancer

Author

Venkatachalam, Annapoorna, primary, Correia, Cristina, additional, Mcgehee, Cordelia, additional, Finstuen-Magro, Sarah, additional, Schneider, Paula A., additional, Hurley, Rachel, additional, Peterson, Kevin L., additional, Heinzen, Ethan, additional, Larson, Melissa C., additional, Hou, Xiaonon, additional, Oberg, Ann L., additional, Weroha, Saravut, additional, and Kaufmann, Scott H., additional

Published
2024
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39. Abstract B012: Transcriptomic insights reveal role of BCL2 proteins in replication checkpoint inhibitor response

Author

Venkatachalam, Annapoorna, primary, Correia, Cristina, additional, Peterson, Kevin L., additional, Hou, Xiaonan, additional, Strathman, Annabella R., additional, Schneider, Paula A, additional, Flatten, Karen S., additional, Duffield, Laura N., additional, McGehee, Cordelia D., additional, Larson, Melissa C., additional, Meng, Xue, additional, Vincelette, Nicole D, additional, Oberg, Ann L., additional, Li, Hu, additional, Weroha, John, additional, and Kaufmann, Scott H, additional

Published
2024
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40. Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer

Author

Chowdhury, Shrabanti, primary, Kennedy, Jacob J., additional, Ivey, Richard G., additional, Murillo, Oscar D., additional, Hosseini, Noshad, additional, Song, Xiaoyu, additional, Petralia, Francesca, additional, Calinawan, Anna, additional, Savage, Sara R., additional, Berry, Anna B., additional, Reva, Boris, additional, Ozbek, Umut, additional, Krek, Azra, additional, Ma, Weiping, additional, da Veiga Leprevost, Felipe, additional, Ji, Jiayi, additional, Yoo, Seungyeul, additional, Lin, Chenwei, additional, Voytovich, Uliana J., additional, Huang, Yajue, additional, Lee, Sun-Hee, additional, Bergan, Lindsay, additional, Lorentzen, Travis D., additional, Mesri, Mehdi, additional, Rodriguez, Henry, additional, Hoofnagle, Andrew N., additional, Herbert, Zachary T., additional, Nesvizhskii, Alexey I., additional, Zhang, Bing, additional, Whiteaker, Jeffrey R., additional, Fenyo, David, additional, McKerrow, Wilson, additional, Wang, Joshua, additional, Schürer, Stephan C., additional, Stathias, Vasileios, additional, Chen, X. Steven, additional, Barcellos-Hoff, Mary Helen, additional, Starr, Timothy K., additional, Winterhoff, Boris J., additional, Nelson, Andrew C., additional, Mok, Samuel C., additional, Kaufmann, Scott H., additional, Drescher, Charles, additional, Cieslik, Marcin, additional, Wang, Pei, additional, Birrer, Michael J., additional, and Paulovich, Amanda G., additional

Published
2024
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41. TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer

Author

Chien, Jeremy, Sicotte, Hugues, Fan, Jian-Bing, Humphray, Sean, Cunningham, Julie M, Kalli, Kimberly R, Oberg, Ann L, Hart, Steven N, Li, Ying, Davila, Jaime I, Baheti, Saurabh, Wang, Chen, Dietmann, Sabine, Atkinson, Elizabeth J, Asmann, Yan W, Bell, Debra A, Ota, Takayo, Tarabishy, Yaman, Kuang, Rui, Bibikova, Marina, Cheetham, R Keira, Grocock, Russell J, Swisher, Elizabeth M, Peden, John, Bentley, David, Kocher, Jean-Pierre A, Kaufmann, Scott H, Hartmann, Lynn C, Shridhar, Viji, and Goode, Ellen L

Subjects
Biological Sciences, Genetics, Cancer, Women's Health, Ovarian Cancer, Rare Diseases, Human Genome, Cancer Genomics, Breast Cancer, 2.1 Biological and endogenous factors, Carcinoma, DNA Primase, Female, Genes, p53, Humans, Loss of Heterozygosity, Mutation, Mutation Rate, Ovarian Neoplasms, Recombinational DNA Repair, Tetraploidy, Environmental Sciences, Information and Computing Sciences, Developmental Biology, Biological sciences, Chemical sciences, Environmental sciences
Abstract

To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC.

Published
2015

43. RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis

Author

Carr, Ryan M., Vorobyev, Denis, Lasho, Terra, Marks, David L., Tolosa, Ezequiel J., Vedder, Alexis, Almada, Luciana L., Yurcheko, Andrey, Padioleau, Ismael, Alver, Bonnie, Coltro, Giacomo, Binder, Moritz, Safgren, Stephanie L., Horn, Isaac, You, Xiaona, Solary, Eric, Balasis, Maria E., Berger, Kurt, Hiebert, James, Witzig, Thomas, Buradkar, Ajinkya, Graf, Temeida, Valent, Peter, Mangaonkar, Abhishek A., Robertson, Keith D., Howard, Matthew T., Kaufmann, Scott H., Pin, Christopher, Fernandez-Zapico, Martin E., Geissler, Klaus, Droin, Nathalie, Padron, Eric, Zhang, Jing, Nikolaev, Sergey, and Patnaik, Mrinal M.

Published
2021
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46. Genes associated with bowel metastases in ovarian cancer

Author

Mariani, Andrea, Wang, Chen, Oberg, Ann L., Riska, Shaun M., Torres, Michelle, Kumka, Joseph, Multinu, Francesco, Sagar, Gunisha, Roy, Debarshi, Jung, Deok–Beom, Zhang, Qing, Grassi, Tommaso, Visscher, Daniel W., Patel, Vatsal P., Jin, Ling, Staub, Julie K., Cliby, William A., Weroha, Saravut J., Kalli, Kimberly R., Hartmann, Lynn C., Kaufmann, Scott H., Goode, Ellen L., and Shridhar, Viji

Published
2019
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47. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial

Author

Konstantinopoulos, Panagiotis A, Barry, William T, Birrer, Michael, Westin, Shannon N, Cadoo, Karen A, Shapiro, Geoffrey I, Mayer, Erica L, O'Cearbhaill, Roisin E, Coleman, Robert L, Kochupurakkal, Bose, Whalen, Christin, Curtis, Jennifer, Farooq, Sarah, Luo, Weixiu, Eismann, Julia, Buss, Mary K, Aghajanian, Carol, Mills, Gordon B, Palakurthi, Sangeetha, Kirschmeier, Paul, Liu, Joyce, Cantley, Lewis C, Kaufmann, Scott H, Swisher, Elizabeth M, D'Andrea, Alan D, Winer, Eric, Wulf, Gerburg M, and Matulonis, Ursula A

Published
2019
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48. 53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer

Author

Hurley, Rachel M., Wahner Hendrickson, Andrea E., Visscher, Daniel W., Ansell, Peter, Harrell, Maria I., Wagner, Jill M., Negron, Vivian, Goergen, Krista M., Maurer, Matthew J., Oberg, Ann L., Meng, X. Wei, Flatten, Karen S., De Jonge, Maja J.A., Van Herpen, Carla D., Gietema, Jourik A., Koornstra, Rutger H.T., Jager, Agnes, den Hollander, Martha W., Dudley, Matthew, Shepherd, Stacie P., Swisher, Elizabeth M., and Kaufmann, Scott H.

Published
2019
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50. Tumorgrafts as In Vivo Surrogates for Women with Ovarian Cancer

Author

Weroha, S John, Becker, Marc A, Enderica-Gonzalez, Sergio, Harrington, Sean C, Oberg, Ann L, Maurer, Matthew J, Perkins, Sarah E, AlHilli, Mariam, Butler, Kristina A, McKinstry, Sarah, Fink, Stephanie, Jenkins, Robert B, Hou, Xiaonan, Kalli, Kimberly R, Goodman, Karin M, Sarkaria, Jann N, Karlan, Beth Y, Kumar, Amanika, Kaufmann, Scott H, Hartmann, Lynn C, and Haluska, Paul

Subjects
Rare Diseases, Ovarian Cancer, Orphan Drug, Cancer, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Animals, Biomarkers, Tumor, Chromosome Aberrations, Cluster Analysis, Comparative Genomic Hybridization, Disease Models, Animal, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Graft Survival, Heterografts, Humans, Mice, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Ovarian Neoplasms, Ultrasonography, Xenograft Model Antitumor Assays, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeOvarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics.Experimental designClinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice.ResultsTumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient.ConclusionsPresented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment.

Published
2014

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