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1. Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

Author

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

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Ovarian Cancer, Rare Diseases, Cancer, Digestive Diseases, Genetics, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Female, Humans, Neoplasm Staging, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Adenocarcinoma, Mucinous, Prognosis, Gastrointestinal Neoplasms, AOCS Group, Australian Pancreatic Genome Initiative, kConFab Investigators, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeAdvanced-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 designDiscovery 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).ResultsInfiltrative 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%).ConclusionsAn 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

2. MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma

Author

Kang, Eun Young, Millstein, Joshua, Popovic, Gordana, Meagher, Nicola S, Bolithon, Adelyn, Talhouk, Aline, Chiu, Derek S, Anglesio, Michael S, Leung, Betty, Tang, Katrina, Lambie, Neil, Pavanello, Marina, Da-anoy, Annalyn, Lambrechts, Diether, Loverix, Liselore, Olbrecht, Siel, Bisinotto, Christiani, Garcia-Donas, Jesus, Ruiz-Llorente, Sergio, Yagüe-Fernandez, Monica, Edwards, Robert P, Elishaev, Esther, Olawaiye, Alexander, Taylor, Sarah, Ataseven, Beyhan, du Bois, Andreas, Harter, Philipp, Lester, Jenny, Høgdall, Claus K, Armasu, Sebastian M, Huang, Yajue, Vierkant, Robert A, Wang, Chen, Winham, Stacey J, Heublein, Sabine, Kommoss, Felix KF, Cramer, Daniel W, Sasamoto, Naoko, van-Wagensveld, Lilian, Lycke, Maria, Mateoiu, Constantina, Joseph, Janine, Pike, Malcolm C, Odunsi, Kunle, Tseng, Chiu-Chen, Pearce, Celeste L, Bilic, Sanela, Conrads, Thomas P, Hartmann, Arndt, Hein, Alexander, Jones, Michael E, Leung, Yee, Beckmann, Matthias W, Ruebner, Matthias, Schoemaker, Minouk J, Terry, Kathryn L, El-Bahrawy, Mona A, Coulson, Penny, Etter, John L, LaVigne-Mager, Katherine, Andress, Juergen, Grube, Marcel, Fischer, Anna, Neudeck, Nina, Robertson, Greg, Farrell, Rhonda, Barlow, Ellen, Quinn, Carmel, Hettiaratchi, Anusha, Casablanca, Yovanni, Erber, Ramona, Stewart, Colin JR, Tan, Adeline, Yu, Yu, Boros, Jessica, Brand, Alison H, Harnett, Paul R, Kennedy, Catherine J, Nevins, Nikilyn, Morgan, Terry, Fasching, Peter A, Vergote, Ignace, Swerdlow, Anthony J, Candido dos Reis, Francisco J, Maxwell, G Larry, Neuhausen, Susan L, Barquin-Garcia, Arantzazu, Modugno, Francesmary, Moysich, Kirsten B, Crowe, Philip J, Hirasawa, Akira, Heitz, Florian, Karlan, Beth Y, Goode, Ellen L, Sinn, Peter, Horlings, Hugo M, Høgdall, Estrid, Sundfeldt, Karin, Kommoss, Stefan, and Staebler, Annette

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Cell Proliferation, Cystadenocarcinoma, Serous, Female, Humans, Ki-67 Antigen, Minichromosome Maintenance Complex Component 3, Ovarian Neoplasms, RNA, Messenger, Survival Rate, High-grade serous carcinoma, Proliferation, MCM3, Clinical Sciences, Pathology, Clinical sciences
Abstract

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p

Published
2022

3. Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer

Author

Hoppe, Michal M, Jaynes, Patrick, Wardyn, Joanna D, Upadhyayula, Sai Srinivas, Tan, Tuan Zea, Lie, Stefanus, Lim, Diana GZ, Pang, Brendan NK, Lim, Sherlly, Yeong, Joe PS, Karnezis, Anthony, Chiu, Derek S, Leung, Samuel, Huntsman, David G, Sedukhina, Anna S, Sato, Ko, Topp, Monique D, Scott, Clare L, Choi, Hyungwon, Patel, Naina R, Brown, Robert, Kaye, Stan B, Pitt, Jason J, Tan, David SP, and Jeyasekharan, Anand D

Subjects
Rare Diseases, Cancer, Genetics, Ovarian Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Carcinoma, Ovarian Epithelial, Female, Humans, Neoplasm Recurrence, Local, Ovarian Neoplasms, Paclitaxel, Platinum, Rad51 Recombinase, HRD, immune exclusion, multiplexed IHC, ovarian cancer, RAD51, Biological Sciences, Medical and Health Sciences
Abstract

Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51-High tumours had shorter progression-free and overall survival compared to RAD51-Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR-proficient cancers (Myriad HRDscore

Published
2021

4. 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, Biotechnology, Rare Diseases, Clinical Research, Genetics, Ovarian Cancer, Cancer, Clinical Trials and Supportive Activities, Detection, screening and diagnosis, 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

5. Molecular characterization of low-grade serous ovarian carcinoma identifies genomic aberrations according to hormone receptor expression

Author

Cheasley, Dane, Fernandez, Marta Llaurado, Köbel, Martin, Kim, Hannah, Dawson, Amy, Hoenisch, Joshua, Bittner, Madison, Chiu, Derek S., Talhouk, Aline, Gilks, C. Blake, Jayawardana, Madawa W., Pishas, Kathleen I., Mes-Masson, Anne-Marie, Provencher, Diane, Nigam, Abhimanyu, Hacker, Neville F., Gorringe, Kylie L., Campbell, Ian G., and Carey, Mark S.

Published
2022
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8. Supplementary Figures S1-S4 from The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Author

Heinze, Karolin, primary, Cairns, Evan S., primary, Thornton, Shelby, primary, Harris, Bronwyn, primary, Milne, Katy, primary, Grube, Marcel, primary, Meyer, Charlotte, primary, Karnezis, Anthony N., primary, Fereday, Sian, primary, Garsed, Dale W., primary, Leung, Samuel C.Y., primary, Chiu, Derek S., primary, Moubarak, Malak, primary, Harter, Philipp, primary, Heitz, Florian, primary, McAlpine, Jessica N., primary, DeFazio, Anna, primary, Bowtell, David D.L., primary, Goode, Ellen L., primary, Pike, Malcolm, primary, Ramus, Susan J., primary, Pearce, C. Leigh, primary, Staebler, Annette, primary, Köbel, Martin, primary, Kommoss, Stefan, primary, Talhouk, Aline, primary, Nelson, Brad H., primary, and Anglesio, Michael S., primary

Published
2023
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9. Supplementary Tables S1-S5 from The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Author

Heinze, Karolin, primary, Cairns, Evan S., primary, Thornton, Shelby, primary, Harris, Bronwyn, primary, Milne, Katy, primary, Grube, Marcel, primary, Meyer, Charlotte, primary, Karnezis, Anthony N., primary, Fereday, Sian, primary, Garsed, Dale W., primary, Leung, Samuel C.Y., primary, Chiu, Derek S., primary, Moubarak, Malak, primary, Harter, Philipp, primary, Heitz, Florian, primary, McAlpine, Jessica N., primary, DeFazio, Anna, primary, Bowtell, David D.L., primary, Goode, Ellen L., primary, Pike, Malcolm, primary, Ramus, Susan J., primary, Pearce, C. Leigh, primary, Staebler, Annette, primary, Köbel, Martin, primary, Kommoss, Stefan, primary, Talhouk, Aline, primary, Nelson, Brad H., primary, and Anglesio, Michael S., primary

Published
2023
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10. Data from The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Author

Heinze, Karolin, primary, Cairns, Evan S., primary, Thornton, Shelby, primary, Harris, Bronwyn, primary, Milne, Katy, primary, Grube, Marcel, primary, Meyer, Charlotte, primary, Karnezis, Anthony N., primary, Fereday, Sian, primary, Garsed, Dale W., primary, Leung, Samuel C.Y., primary, Chiu, Derek S., primary, Moubarak, Malak, primary, Harter, Philipp, primary, Heitz, Florian, primary, McAlpine, Jessica N., primary, DeFazio, Anna, primary, Bowtell, David D.L., primary, Goode, Ellen L., primary, Pike, Malcolm, primary, Ramus, Susan J., primary, Pearce, C. Leigh, primary, Staebler, Annette, primary, Köbel, Martin, primary, Kommoss, Stefan, primary, Talhouk, Aline, primary, Nelson, Brad H., primary, and Anglesio, Michael S., primary

Published
2023
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11. TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma

Author

Ennishi, Daisuke, Healy, Shannon, Bashashati, Ali, Saberi, Saeed, Hother, Christoffer, Mottok, Anja, Chan, Fong Chun, Chong, Lauren, Abraham, Libin, Kridel, Robert, Boyle, Merrill, Meissner, Barbara, Aoki, Tomohiro, Takata, Katsuyoshi, Woolcock, Bruce W., Viganò, Elena, Gold, Michael, Molday, Laurie L., Molday, Robert S., Telenius, Adele, Li, Michael Y., Wretham, Nicole, Dos Santos, Nancy, Wong, Mark, Viller, Natasja N., Uger, Robert A., Duns, Gerben, Baticados, Abigail, Madero, Angel, Bristow, Brianna N., Farinha, Pedro, Slack, Graham W., Ben-Neriah, Susana, Lai, Daniel, Zhang, Allen W., Salehi, Sohrab, Shulha, Hennady P., Chiu, Derek S., Mostafavi, Sara, Gerrie, Alina S., Huang, Da Wei, Rushton, Christopher, Villa, Diego, Sehn, Laurie H., Savage, Kerry J., Mungall, Andrew J., Weng, Andrew P., Bally, Marcel B., Morin, Ryan D., Cohen Freue, Gabriela V., Staudt, Louis M., Connors, Joseph M., Marra, Marco A., Shah, Sohrab P., Gascoyne, Randy D., Scott, David W., and Steidl, Christian

Published
2020
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12. The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Author

Heinze, Karolin, primary, Cairns, Evan S., additional, Thornton, Shelby, additional, Harris, Bronwyn, additional, Milne, Katy, additional, Grube, Marcel, additional, Meyer, Charlotte, additional, Karnezis, Anthony N., additional, Fereday, Sian, additional, Garsed, Dale W., additional, Leung, Samuel C.Y., additional, Chiu, Derek S., additional, Moubarak, Malak, additional, Harter, Philipp, additional, Heitz, Florian, additional, McAlpine, Jessica N., additional, DeFazio, Anna, additional, Bowtell, David D.L., additional, Goode, Ellen L., additional, Pike, Malcolm, additional, Ramus, Susan J., additional, Pearce, C. Leigh, additional, Staebler, Annette, additional, Köbel, Martin, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Nelson, Brad H., additional, and Anglesio, Michael S., additional

Published
2023
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14. NACT Supplementary Tables - revised from Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy

Author

Lo, Charlotte S., primary, Sanii, Sanaz, primary, Kroeger, David R., primary, Milne, Katy, primary, Talhouk, Aline, primary, Chiu, Derek S., primary, Rahimi, Kurosh, primary, Shaw, Patricia A., primary, Clarke, Blaise A., primary, and Nelson, Brad H., primary

Published
2023
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15. NACT Supplementary Figures - revised from Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy

Author

Lo, Charlotte S., primary, Sanii, Sanaz, primary, Kroeger, David R., primary, Milne, Katy, primary, Talhouk, Aline, primary, Chiu, Derek S., primary, Rahimi, Kurosh, primary, Shaw, Patricia A., primary, Clarke, Blaise A., primary, and Nelson, Brad H., primary

Published
2023
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16. Supplementary Data from Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma

Author

Krämer, Pauline, primary, Talhouk, Aline, primary, Brett, Mary Anne, primary, Chiu, Derek S., primary, Cairns, Evan S., primary, Scheunhage, Daniëlla A., primary, Hammond, Rory F.L., primary, Farnell, David, primary, Nazeran, Tayyebeh M., primary, Grube, Marcel, primary, Xia, Zhouchunyang, primary, Senz, Janine, primary, Leung, Samuel, primary, Feil, Lukas, primary, Pasternak, Jana, primary, Dixon, Katherine, primary, Hartkopf, Andreas, primary, Krämer, Bernhard, primary, Brucker, Sara, primary, Heitz, Florian, primary, du Bois, Andreas, primary, Harter, Philipp, primary, Kommoss, Felix K.F., primary, Sinn, Hans-Peter, primary, Heublein, Sabine, primary, Kommoss, Friedrich, primary, Vollert, Hans-Walter, primary, Manchanda, Ranjit, primary, de Kroon, Cornelis D., primary, Nijman, Hans W., primary, de Bruyn, Marco, primary, Thompson, Emily F., primary, Bashashati, Ali, primary, McAlpine, Jessica N., primary, Singh, Naveena, primary, Tinker, Anna V., primary, Staebler, Annette, primary, Bosse, Tjalling, primary, Kommoss, Stefan, primary, Köbel, Martin, primary, and Anglesio, Michael S., primary

Published
2023
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17. Profiling the immune landscape in mucinous ovarian carcinoma

Author

Meagher, Nicola S., primary, Hamilton, Phineas, additional, Milne, Katy, additional, Thornton, Shelby, additional, Harris, Bronwyn, additional, Weir, Ashley, additional, Alsop, Jennifer, additional, Bisinoto, Christiani, additional, Brenton, James D., additional, Brooks-Wilson, Angela, additional, Chiu, Derek S., additional, Cushing-Haugen, Kara L., additional, Fereday, Sian, additional, Garsed, Dale W., additional, Gayther, Simon A., additional, Gentry-Maharaj, Aleksandra, additional, Gilks, Blake, additional, Jimenez-Linan, Mercedes, additional, Kennedy, Catherine J., additional, Le, Nhu D., additional, Piskorz, Anna M., additional, Riggan, Marjorie J., additional, Shah, Mitul, additional, Singh, Naveena, additional, Talhouk, Aline, additional, Widschwendter, Martin, additional, Bowtell, David D.L., additional, Candido dos Reis, Francisco J., additional, Cook, Linda S., additional, Fortner, Renée T., additional, García, María J., additional, Harris, Holly R., additional, Huntsman, David G., additional, Karnezis, Anthony N., additional, Köbel, Martin, additional, Menon, Usha, additional, Pharoah, Paul D.P., additional, Doherty, Jennifer A., additional, Anglesio, Michael S., additional, Pike, Malcolm C., additional, Pearce, Celeste Leigh, additional, Friedlander, Michael L., additional, DeFazio, Anna, additional, Nelson, Brad H., additional, and Ramus, Susan J., additional

Published
2023
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18. Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8+ TIL infiltration, and provides no independent prognostic value in endometriosis‐associated ovarian carcinomas

Author

Heinze, Karolin, primary, Nazeran, Tayyebeh M, additional, Lee, Sandra, additional, Krämer, Pauline, additional, Cairns, Evan S, additional, Chiu, Derek S, additional, Leung, Samuel CY, additional, Kang, Eun Young, additional, Meagher, Nicola S, additional, Kennedy, Catherine J, additional, Boros, Jessica, additional, Kommoss, Friedrich, additional, Vollert, Hans‐Walter, additional, Heitz, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Grube, Marcel, additional, Kraemer, Bernhard, additional, Staebler, Annette, additional, Kommoss, Felix KF, additional, Heublein, Sabine, additional, Sinn, Hans‐Peter, additional, Singh, Naveena, additional, Laslavic, Angela, additional, Elishaev, Esther, additional, Olawaiye, Alex, additional, Moysich, Kirsten, additional, Modugno, Francesmary, additional, Sharma, Raghwa, additional, Brand, Alison H, additional, Harnett, Paul R, additional, DeFazio, Anna, additional, Fortner, Renée T, additional, Lubinski, Jan, additional, Lener, Marcin, additional, Tołoczko‐Grabarek, Aleksandra, additional, Cybulski, Cezary, additional, Gronwald, Helena, additional, Gronwald, Jacek, additional, Coulson, Penny, additional, El‐Bahrawy, Mona A, additional, Jones, Michael E, additional, Schoemaker, Minouk J, additional, Swerdlow, Anthony J, additional, Gorringe, Kylie L, additional, Campbell, Ian, additional, Cook, Linda, additional, Gayther, Simon A, additional, Carney, Michael E, additional, Shvetsov, Yurii B, additional, Hernandez, Brenda Y, additional, Wilkens, Lynne R, additional, Goodman, Marc T, additional, Mateoiu, Constantina, additional, Linder, Anna, additional, Sundfeldt, Karin, additional, Kelemen, Linda E, additional, Gentry‐Maharaj, Aleksandra, additional, Widschwendter, Martin, additional, Menon, Usha, additional, Bolton, Kelly L, additional, Alsop, Jennifer, additional, Shah, Mitul, additional, Jimenez‐Linan, Mercedes, additional, Pharoah, Paul DP, additional, Brenton, James D, additional, Cushing‐Haugen, Kara L, additional, Harris, Holly R, additional, Doherty, Jennifer A, additional, Gilks, Blake, additional, Ghatage, Prafull, additional, Huntsman, David G, additional, Nelson, Gregg S, additional, Tinker, Anna V, additional, Lee, Cheng‐Han, additional, Goode, Ellen L, additional, Nelson, Brad H, additional, Ramus, Susan J, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Köbel, Martin, additional, and Anglesio, Michael S, additional

Published
2022
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19. MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma

Author

Kang, Eun Young, primary, Millstein, Joshua, additional, Popovic, Gordana, additional, Meagher, Nicola S., additional, Bolithon, Adelyn, additional, Talhouk, Aline, additional, Chiu, Derek S., additional, Anglesio, Michael S., additional, Leung, Betty, additional, Tang, Katrina, additional, Lambie, Neil, additional, Pavanello, Marina, additional, Da-anoy, Annalyn, additional, Lambrechts, Diether, additional, Loverix, Liselore, additional, Olbrecht, Siel, additional, Bisinotto, Christiani, additional, Garcia-Donas, Jesus, additional, Ruiz-Llorente, Sergio, additional, Yagüe-Fernandez, Monica, additional, Edwards, Robert P., additional, Elishaev, Esther, additional, Olawaiye, Alexander, additional, Taylor, Sarah, additional, Ataseven, Beyhan, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Lester, Jenny, additional, Høgdall, Claus K., additional, Armasu, Sebastian M., additional, Huang, Yajue, additional, Vierkant, Robert A., additional, Wang, Chen, additional, Winham, Stacey J., additional, Heublein, Sabine, additional, Kommoss, Felix K. F., additional, Cramer, Daniel W., additional, Sasamoto, Naoko, additional, van-Wagensveld, Lilian, additional, Lycke, Maria, additional, Mateoiu, Constantina, additional, Joseph, Janine, additional, Pike, Malcolm C., additional, Odunsi, Kunle, additional, Tseng, Chiu-Chen, additional, Pearce, Celeste L., additional, Bilic, Sanela, additional, Conrads, Thomas P., additional, Hartmann, Arndt, additional, Hein, Alexander, additional, Jones, Michael E., additional, Leung, Yee, additional, Beckmann, Matthias W., additional, Ruebner, Matthias, additional, Schoemaker, Minouk J., additional, Terry, Kathryn L., additional, El-Bahrawy, Mona A., additional, Coulson, Penny, additional, Etter, John L., additional, LaVigne-Mager, Katherine, additional, Andress, Juergen, additional, Grube, Marcel, additional, Fischer, Anna, additional, Neudeck, Nina, additional, Robertson, Greg, additional, Farrell, Rhonda, additional, Barlow, Ellen, additional, Quinn, Carmel, additional, Hettiaratchi, Anusha, additional, Casablanca, Yovanni, additional, Erber, Ramona, additional, Stewart, Colin J. R., additional, Tan, Adeline, additional, Yu, Yu, additional, Boros, Jessica, additional, Brand, Alison H., additional, Harnett, Paul R., additional, Kennedy, Catherine J., additional, Nevins, Nikilyn, additional, Morgan, Terry, additional, Fasching, Peter A., additional, Vergote, Ignace, additional, Swerdlow, Anthony J., additional, Candido dos Reis, Francisco J., additional, Maxwell, G. Larry, additional, Neuhausen, Susan L., additional, Barquin-Garcia, Arantzazu, additional, Modugno, Francesmary, additional, Moysich, Kirsten B., additional, Crowe, Philip J., additional, Hirasawa, Akira, additional, Heitz, Florian, additional, Karlan, Beth Y., additional, Goode, Ellen L., additional, Sinn, Peter, additional, Horlings, Hugo M., additional, Høgdall, Estrid, additional, Sundfeldt, Karin, additional, Kommoss, Stefan, additional, Staebler, Annette, additional, Wu, Anna H., additional, Cohen, Paul A., additional, DeFazio, Anna, additional, Lee, Cheng-Han, additional, Steed, Helen, additional, Le, Nhu D., additional, Gayther, Simon A., additional, Lawrenson, Kate, additional, Pharoah, Paul D. P., additional, Konecny, Gottfried, additional, Cook, Linda S., additional, Ramus, Susan J., additional, Kelemen, Linda E., additional, and Köbel, Martin, additional

Published
2021
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20. Prognostic and Immunological Significance of ARID1A Status in Endometriosis-Associated Ovarian Carcinoma

Author

Heinze, Karolin, primary, Nazeran, Tayyebeh M, additional, Lee, Sandra, additional, Kraemer, Pauline, additional, Cairns, Evan S, additional, Chiu, Derek S, additional, Leung, Samuel CY, additional, Kang, Eun-Young, additional, Meagher, Nicola S, additional, Kennedy, Catherine J, additional, Boros, Jessica, additional, Kommoss, Friedrich, additional, Vollert, Hans-Walter, additional, Heitze, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Grube, Marcel, additional, Kraemer, Bernhard, additional, Staebler, Annette, additional, Kommoss, Felix K.F, additional, Heublein, Sabine, additional, Sinn, Peter, additional, Singh, Naveena, additional, Laslavic, Angela, additional, Elishaev, Esther, additional, Olawaiye, Alex, additional, Moysich, Kirsten, additional, Modugno, Francesmary, additional, Sharma, Raghwa, additional, Brand, Alison H, additional, Harnett, Paul R, additional, deFazio, Anna, additional, Fortner, Renee T, additional, Lubinski, Jan, additional, Lener, Marcin, additional, Toloczko-Grabarek, Aleksandra, additional, Cybulski, Cezary, additional, Gronwald, Helena, additional, Gronwald, Jacek, additional, Coulson, Penny, additional, El-Bahrawy, Mona A, additional, Jones, Michael E, additional, Schoemaker, Minouk J, additional, Swerdlow, Anthony J, additional, Gorringe, Kylie L, additional, Campbell, Ian, additional, Cook, Linda, additional, Gayther, Simon A, additional, Carney, Michael E, additional, Shvetsov, Yurii B, additional, Hernandez, Brenda B, additional, Wilkens, Lynne R, additional, Goodman, Marc T, additional, Mateoiu, Constantina, additional, Linder, Anna, additional, Sundfeldt, Karin, additional, Kelemen, Linda E, additional, Gentry-Maharaj, Aleksandra, additional, Widschwendter, Martin, additional, Menon, Usha, additional, Bolton, Kelly L, additional, Alsop, Jennifer, additional, Shah, Mitul, additional, Jimenez-Linan, Mercedes, additional, Pharoah, Paul DP, additional, Brenton, James D, additional, Cushing-Haugen, Kara L, additional, Harris, Holly R, additional, Doherty, Jennifer A, additional, Gilks, Blake, additional, Ghatage, Prafull, additional, Huntsman, David G, additional, Nelson, Gregg S, additional, Tinker, Anna V, additional, Lee, Cheng-Han, additional, Goode, Ellen L, additional, Nelson, Brad H, additional, Ramus, Susan J, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Koebel, Martin, additional, and Anglesio, Michael S, additional

Published
2021
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21. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis

Author

McAlpine, Jessica N., primary, Chiu, Derek S., additional, Nout, Remi A., additional, Church, David N., additional, Schmidt, Pascal, additional, Lam, Stephanie, additional, Leung, Samuel, additional, Bellone, Stefania, additional, Wong, Adele, additional, Brucker, Sara Y., additional, Lee, Cheng Han, additional, Clarke, Blaise A., additional, Huntsman, David G., additional, Bernardini, Marcus Q., additional, Ngeow, Joanne, additional, Santin, Alessandro D., additional, Goodfellow, Paul, additional, Levine, Douglas A., additional, Köbel, Martin, additional, Kommoss, Stefan, additional, Bosse, Tjalling, additional, Gilks, C. Blake, additional, and Talhouk, Aline, additional

Published
2021
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22. Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8+ TIL infiltration, and provides no independent prognostic value in endometriosis‐associated ovarian carcinomas.

Author

Heinze, Karolin, Nazeran, Tayyebeh M, Lee, Sandra, Krämer, Pauline, Cairns, Evan S, Chiu, Derek S, Leung, Samuel CY, Kang, Eun Young, Meagher, Nicola S, Kennedy, Catherine J, Boros, Jessica, Kommoss, Friedrich, Vollert, Hans‐Walter, Heitz, Florian, du Bois, Andreas, Harter, Philipp, Grube, Marcel, Kraemer, Bernhard, Staebler, Annette, and Kommoss, Felix KF

Subjects
OVARIAN cancer, PROGNOSIS, DNA mismatch repair, SINGLE nucleotide polymorphisms, BIOMARKERS, CARCINOMA
Abstract

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis‐associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour‐infiltrating lymphocytes (CD8+ TILs), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOCs and 25% of ENOCs. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p = 0.012) and was associated with MMRd (p < 0.001) and the presence of CD8+ TILs (p = 0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOCs we also observed an association with ARID1A loss‐of‐function mutation as a result of small indels (p = 0.035, versus single nucleotide variants). In ENOC, the association with ARID1A loss, CD8+ TILs, and age appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss‐of‐function mutations in endometriosis‐associated ovarian cancers and brings clarity to the prognostic significance. © 2021 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma

Author

Krämer, Pauline, primary, Talhouk, Aline, additional, Brett, Mary Anne, additional, Chiu, Derek S., additional, Cairns, Evan S., additional, Scheunhage, Daniëlla A., additional, Hammond, Rory F.L., additional, Farnell, David, additional, Nazeran, Tayyebeh M., additional, Grube, Marcel, additional, Xia, Zhouchunyang, additional, Senz, Janine, additional, Leung, Samuel, additional, Feil, Lukas, additional, Pasternak, Jana, additional, Dixon, Katherine, additional, Hartkopf, Andreas, additional, Krämer, Bernhard, additional, Brucker, Sara, additional, Heitz, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Kommoss, Felix K.F., additional, Sinn, Hans-Peter, additional, Heublein, Sabine, additional, Kommoss, Friedrich, additional, Vollert, Hans-Walter, additional, Manchanda, Ranjit, additional, de Kroon, Cornelis D., additional, Nijman, Hans W., additional, de Bruyn, Marco, additional, Thompson, Emily F., additional, Bashashati, Ali, additional, McAlpine, Jessica N., additional, Singh, Naveena, additional, Tinker, Anna V., additional, Staebler, Annette, additional, Bosse, Tjalling, additional, Kommoss, Stefan, additional, Köbel, Martin, additional, and Anglesio, Michael S., additional

Published
2020
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24. Primary platinum resistance and immune exclusion in ovarian carcinomas with high expression of the homologous recombination mediator RAD51

Author

Hoppe, Michal M., primary, Tan, Tuan Zea, additional, Lie, Stefanus, additional, Lim, Sherlly, additional, Yeong, Joe PS, additional, Wardyn, Joanna D., additional, Jaynes, Patrick, additional, Lim, Diana GZ, additional, Pang, Brendan NK, additional, Karnezis, Anthony, additional, Chiu, Derek S., additional, Leung, Samuel, additional, Huntsman, David G., additional, Sedukhina, Anna S., additional, Sato, Ko, additional, Kaye, Stan, additional, Choi, Hyungwon, additional, Patel, Naina, additional, Brown, Robert, additional, Pitt, Jason J., additional, Tan, David SP, additional, and Jeyasekharan, Anand D., additional

Published
2020
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26. Abstract 3480:TMEM30Aloss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma

Author

Healy, Shannon, primary, Ennishi, Daisuke, additional, Bashashati, Ali, additional, Saberi, Saeed, additional, Hother, Christoffer, additional, Mottok, Anja, additional, Chan, Fong Chun, additional, Chong, Lauren, additional, Kridel, Robert, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Aoki, Tomohiro, additional, Takata, Katsuyoshi, additional, Woolcock, Bruce W., additional, Vigano, Elena, additional, Abraham, Libin, additional, Gold, Michael, additional, Telenius, Adele, additional, Farinha, Pedro, additional, Slack, Graham, additional, Ben-Neriah, Susana, additional, Lai, Daniel, additional, Zhang, Allen W., additional, Salehi, Sohrab, additional, Shulha, Hennady P., additional, Chiu, Derek S., additional, Mostafavi, Sara, additional, Gerrie, Alina S., additional, Villa, Diego, additional, Sehn, Laurie H., additional, Savage, Kerry J. J., additional, Mungall, Andrew J. J., additional, Weng, Andrew P., additional, Bally, Marcel, additional, Morin, Ryan D., additional, Freue, Gabriela V. Cohen, additional, Connors, Joseph M., additional, Marra, Marco A., additional, Shah, Sohrab P., additional, Gascoyne, Randy D., additional, Scott, David W., additional, Steidl, Christian, additional, and Steidl, Ulrich, additional

Published
2019
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27. Clinicopathologic Characteristics of Mesonephric Adenocarcinomas and Mesonephric-like Adenocarcinomas in the Gynecologic Tract

Author

Pors, Jennifer, Segura, Sheila, Chiu, Derek S., Almadani, Noorah, Ren, Hezhen, Fix, Daniel J., Howitt, Brooke E., Kolin, David, McCluggage, W. Glenn, Mirkovic, Jelena, Gilks, Blake, Park, Kay J., and Hoang, Lynn

Abstract

Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are uncommon neoplasms of the gynecologic tract that have until recently been poorly understood. Although their morphologic, immunohistochemical, and molecular profiles have been recently defined, little is known about their clinical behavior. Small studies have demonstrated inconsistent findings and no large studies have examined the clinical behavior of these adenocarcinomas. In this multi-institutional study, representing the largest and most stringently defined cohort of cases to date, we examined the clinicopathologic features of 99 MAs and MLAs (30 MAs of the uterine cervix, 44 MLAs of the endometrium, and 25 MLAs of the ovary). Only tumors with characteristic mesonephric morphology and either immunohistochemical or molecular support were included. Our results demonstrate that the majority of mesonephric neoplasms presented at an advanced stage (II to IV) (15/25 [60%] MA of the cervix, 25/43 [58%] MLA of the endometrium, and 7/18 [39%] MLA of the ovary). The majority (46/89 [52%] overall, 12/24 [50%] MA of the cervix, 24/41 [59%] MLA of the endometrium, and 10/24 [42%] MLA of the ovary) developed recurrences, most commonly distant (9/12 [75%] MA of the cervix, 22/24 [92%] MLA of the endometrium, and 5/9 [56%] MLA of the ovary). The 5-year disease-specific survival was 74% (n=26) for MA of cervix, 72% (n=43) for MLA of endometrium, and 71% (n=23) for MLA of ovary. Our results confirm that mesonephric neoplasms are a clinically aggressive group of gynecologic carcinomas that typically present at an advanced stage, with a predilection for pulmonary recurrence.

Published
2024
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29. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

Author

Xu, Hong, primary, Di Antonio, Marco, additional, McKinney, Steven, additional, Mathew, Veena, additional, Ho, Brandon, additional, O’Neil, Nigel J., additional, Santos, Nancy Dos, additional, Silvester, Jennifer, additional, Wei, Vivien, additional, Garcia, Jessica, additional, Kabeer, Farhia, additional, Lai, Daniel, additional, Soriano, Priscilla, additional, Banáth, Judit, additional, Chiu, Derek S., additional, Yap, Damian, additional, Le, Daniel D., additional, Ye, Frank B., additional, Zhang, Anni, additional, Thu, Kelsie, additional, Soong, John, additional, Lin, Shu-chuan, additional, Tsai, Angela Hsin Chin, additional, Osako, Tomo, additional, Algara, Teresa, additional, Saunders, Darren N., additional, Wong, Jason, additional, Xian, Jian, additional, Bally, Marcel B., additional, Brenton, James D., additional, Brown, Grant W., additional, Shah, Sohrab P., additional, Cescon, David, additional, Mak, Tak W., additional, Caldas, Carlos, additional, Stirling, Peter C., additional, Hieter, Phil, additional, Balasubramanian, Shankar, additional, and Aparicio, Samuel, additional

Published
2017
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31. TMEM30Aloss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma

Author

Ennishi, Daisuke, Healy, Shannon, Bashashati, Ali, Saberi, Saeed, Hother, Christoffer, Mottok, Anja, Chan, Fong Chun, Chong, Lauren, Abraham, Libin, Kridel, Robert, Boyle, Merrill, Meissner, Barbara, Aoki, Tomohiro, Takata, Katsuyoshi, Woolcock, Bruce W., Viganò, Elena, Gold, Michael, Molday, Laurie L., Molday, Robert S., Telenius, Adele, Li, Michael Y., Wretham, Nicole, Dos Santos, Nancy, Wong, Mark, Viller, Natasja N., Uger, Robert A., Duns, Gerben, Baticados, Abigail, Madero, Angel, Bristow, Brianna N., Farinha, Pedro, Slack, Graham W., Ben-Neriah, Susana, Lai, Daniel, Zhang, Allen W., Salehi, Sohrab, Shulha, Hennady P., Chiu, Derek S., Mostafavi, Sara, Gerrie, Alina S., Huang, Da Wei, Rushton, Christopher, Villa, Diego, Sehn, Laurie H., Savage, Kerry J., Mungall, Andrew J., Weng, Andrew P., Bally, Marcel B., Morin, Ryan D., Cohen Freue, Gabriela V., Staudt, Louis M., Connors, Joseph M., Marra, Marco A., Shah, Sohrab P., Gascoyne, Randy D., Scott, David W., and Steidl, Christian

Abstract

Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and ‘eat-me’ signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30Aloss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL. Using TMEM30A-knockout systems, increased accumulation of chemotherapy drugs was observed in TMEM30A-knockout cell lines and TMEM30A-mutated primary cells, explaining the improved treatment outcome. Furthermore, we found increased tumor-associated macrophages and an enhanced effect of anti-CD47 blockade limiting tumor growth in TMEM30A-knockout models. By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following antigen stimulation—a mechanism conferring selective advantage during B-cell lymphoma development. Our data highlight a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterize intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited.

Published
2020
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32. Single-Patient Molecular Testing with NanoString nCounter Data Using a Reference-Based Strategy for Batch Effect Correction

Author

Talhouk, Aline, primary, Kommoss, Stefan, additional, Mackenzie, Robertson, additional, Cheung, Martin, additional, Leung, Samuel, additional, Chiu, Derek S., additional, Kalloger, Steve E., additional, Huntsman, David G., additional, Chen, Stephanie, additional, Intermaggio, Maria, additional, Gronwald, Jacek, additional, Chan, Fong C., additional, Ramus, Susan J., additional, Steidl, Christian, additional, Scott, David W., additional, and Anglesio, Michael S., additional

Published
2016
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33. Person-Generated Health Data in Women's Health: Scoping Review.

Author

Karim JL, Wan R, Tabet RS, Chiu DS, and Talhouk A

Subjects
Humans, Female, Patient Generated Health Data, COVID-19 epidemiology, Pregnancy, Women's Health
Abstract

Background: The increased pervasiveness of digital health technology is producing large amounts of person-generated health data (PGHD). These data can empower people to monitor their health to promote prevention and management of disease. Women make up one of the largest groups of consumers of digital self-tracking technology., Objective: In this scoping review, we aimed to (1) identify the different areas of women's health monitored using PGHD from connected health devices, (2) explore personal metrics collected through these technologies, and (3) synthesize facilitators of and barriers to women's adoption and use of connected health devices., Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews, we searched 5 databases for articles published between January 1, 2015, and February 29, 2020. Papers were included if they targeted women or female individuals and incorporated digital health tools that collected PGHD outside a clinical setting., Results: We included a total of 406 papers in this review. Articles on the use of PGHD for women steadily increased from 2015 to 2020. The health areas that the articles focused on spanned several topics, with pregnancy and the postpartum period being the most prevalent followed by cancer. Types of digital health used to collect PGHD included mobile apps, wearables, websites, the Internet of Things or smart devices, 2-way messaging, interactive voice response, and implantable devices. A thematic analysis of 41.4% (168/406) of the papers revealed 6 themes regarding facilitators of and barriers to women's use of digital health technology for collecting PGHD: (1) accessibility and connectivity, (2) design and functionality, (3) accuracy and credibility, (4) audience and adoption, (5) impact on community and health service, and (6) impact on health and behavior., Conclusions: Leading up to the COVID-19 pandemic, the adoption of digital health tools to address women's health concerns was on a steady rise. The prominence of tools related to pregnancy and the postpartum period reflects the strong focus on reproductive health in women's health research and highlights opportunities for digital technology development in other women's health topics. Digital health technology was most acceptable when it was relevant to the target audience, was seen as user-friendly, and considered women's personalization preferences while also ensuring accuracy of measurements and credibility of information. The integration of digital technologies into clinical care will continue to evolve, and factors such as liability and health care provider workload need to be considered. While acknowledging the diversity of individual needs, the use of PGHD can positively impact the self-care management of numerous women's health journeys. The COVID-19 pandemic has ushered in increased adoption and acceptance of digital health technology. This study could serve as a baseline comparison for how this field has evolved as a result., International Registered Report Identifier (irrid): RR2-10.2196/26110., (©Jalisa Lynn Karim, Rachel Wan, Rhea S Tabet, Derek S Chiu, Aline Talhouk. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 16.05.2024.)

Published
2024
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34. Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8 + TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.

Author

Heinze K, Nazeran TM, Lee S, Krämer P, Cairns ES, Chiu DS, Leung SC, Kang EY, Meagher NS, Kennedy CJ, Boros J, Kommoss F, Vollert HW, Heitz F, du Bois A, Harter P, Grube M, Kraemer B, Staebler A, Kommoss FK, Heublein S, Sinn HP, Singh N, Laslavic A, Elishaev E, Olawaiye A, Moysich K, Modugno F, Sharma R, Brand AH, Harnett PR, DeFazio A, Fortner RT, Lubinski J, Lener M, Tołoczko-Grabarek A, Cybulski C, Gronwald H, Gronwald J, Coulson P, El-Bahrawy MA, Jones ME, Schoemaker MJ, Swerdlow AJ, Gorringe KL, Campbell I, Cook L, Gayther SA, Carney ME, Shvetsov YB, Hernandez BY, Wilkens LR, Goodman MT, Mateoiu C, Linder A, Sundfeldt K, Kelemen LE, Gentry-Maharaj A, Widschwendter M, Menon U, Bolton KL, Alsop J, Shah M, Jimenez-Linan M, Pharoah PD, Brenton JD, Cushing-Haugen KL, Harris HR, Doherty JA, Gilks B, Ghatage P, Huntsman DG, Nelson GS, Tinker AV, Lee CH, Goode EL, Nelson BH, Ramus SJ, Kommoss S, Talhouk A, Köbel M, and Anglesio MS

Subjects
Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Brain Neoplasms, CD8-Positive T-Lymphocytes pathology, Canada, Colorectal Neoplasms, DNA-Binding Proteins genetics, Female, Humans, Neoplastic Syndromes, Hereditary, Nuclear Proteins genetics, Prognosis, Transcription Factors genetics, Carcinoma, Endometriosis genetics, Endometriosis pathology, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology
Abstract

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis-associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8 + tumour-infiltrating lymphocytes (CD8 + TILs), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOCs and 25% of ENOCs. We found no associations between ARID1A loss and outcomes, stage, age, or CD8 + TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p = 0.012) and was associated with MMRd (p < 0.001) and the presence of CD8 + TILs (p = 0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOCs we also observed an association with ARID1A loss-of-function mutation as a result of small indels (p = 0.035, versus single nucleotide variants). In ENOC, the association with ARID1A loss, CD8 + TILs, and age appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8 + TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. © 2021 The Pathological Society of Great Britain and Ireland., (© 2021 The Pathological Society of Great Britain and Ireland.)

Published
2022
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