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4. Single-cell genomic variation induced by mutational processes in cancer

Author

Funnell, Tyler, O’Flanagan, Ciara H., Williams, Marc J., McPherson, Andrew, McKinney, Steven, Kabeer, Farhia, Lee, Hakwoo, Salehi, Sohrab, Vázquez-García, Ignacio, Shi, Hongyu, Leventhal, Emily, Masud, Tehmina, Eirew, Peter, Yap, Damian, Zhang, Allen W., Lim, Jamie L. P., Wang, Beixi, Brimhall, Jazmine, Biele, Justina, Ting, Jerome, Au, Vinci, Van Vliet, Michael, Liu, Yi Fei, Beatty, Sean, Lai, Daniel, Pham, Jenifer, Grewal, Diljot, Abrams, Douglas, Havasov, Eliyahu, Leung, Samantha, Bojilova, Viktoria, Moore, Richard A., Rusk, Nicole, Uhlitz, Florian, Ceglia, Nicholas, Weiner, Adam C., Zaikova, Elena, Douglas, J. Maxwell, Zamarin, Dmitriy, Weigelt, Britta, Kim, Sarah H., Da Cruz Paula, Arnaud, Reis-Filho, Jorge S., Martin, Spencer D., Li, Yangguang, Xu, Hong, de Algara, Teresa Ruiz, Lee, So Ra, Llanos, Viviana Cerda, Huntsman, David G., McAlpine, Jessica N., Shah, Sohrab P., and Aparicio, Samuel

Published
2022
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5. Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification

Author

Thompson, Emily F., Huvila, Jutta, Jamieson, Amy, Leung, Samuel, Lum, Amy, Offman, Saul, Lytwyn, Alice, Sur, Mona Lisa, Hoang, Lynn, Irving, Julie, van der Westhuizen, Nicholas, Morin, Chantale, Bicamumpaka, Cyrille, Azordegan, Nazilla, Gougeon, François, Ennour-Idrissi, Kaoutar, Senz, Janine, McConechy, Melissa K., Aguirre-Hernandez, Rosalia, Lui, Victoria, Kuo, Carolyn, Bell, Cassidy, Salisbury, Taylor, Lawson, James, He, Ellen, Wang, Shanzhao, Chiu, Derek, Kean, Sarah, Samouëlian, Vanessa, Salvador, Shannon, Gotlieb, Walter, Helpman, Limor, Scott, Stephanie, Wohlmuth, Christoph, Vicus, Danielle, Plante, Marie, Talhouk, Aline, Huntsman, David, Parra-Herran, Carlos, Kinloch, Mary, Grondin, Katherine, Gilks, C. Blake, and McAlpine, Jessica N.

Published
2022
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6. AI-based histopathology image analysis reveals a distinct subset of endometrial cancers

Author

Darbandsari, Amirali, Farahani, Hossein, Asadi, Maryam, Wiens, Matthew, Cochrane, Dawn, Khajegili Mirabadi, Ali, Jamieson, Amy, Farnell, David, Ahmadvand, Pouya, Douglas, Maxwell, Leung, Samuel, Abolmaesumi, Purang, Jones, Steven J. M., Talhouk, Aline, Kommoss, Stefan, Gilks, C. Blake, Huntsman, David G., Singh, Naveena, McAlpine, Jessica N., and Bashashati, Ali

Published
2024
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8. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers

Author

Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise A, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, May, Taymaa, McAlpine, Jessica N, and McGuire, Valerie

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Human Genome, Uterine Cancer, Genetics, Biotechnology, Ovarian Cancer, Prevention, Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Endometrial Neoplasms, Female, Genome-Wide Association Study, Humans, Ovarian Neoplasms, Quantitative Trait Loci, Risk Factors, OPAL Study Group, AOCS Group, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAccumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.MethodsUsing LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.ResultsGenetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.ConclusionsUsing cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.ImpactOur research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

Published
2021

10. Molecular subtype stratified outcomes according to adjuvant therapy in endometrial cancer

Author

Jamieson, Amy, Huvila, Jutta, Leung, Samuel, Chiu, Derek, Thompson, Emily F., Lum, Amy, Kinloch, Mary, Helpman, Limor, Salvador, Shannon, Vicus, Danielle, Kean, Sarah, Samouelian, Vanessa, Grondin, Katherine, Irving, Julie, Offman, Saul, Parra-Herran, Carlos, Lau, Susie, Scott, Stephanie, Plante, Marie, McConechy, Melissa K., Huntsman, David G., Talhouk, Aline, Kommoss, Stefan, Gilks, C. Blake, and McAlpine, Jessica N.

Published
2023
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11. Arginine Depletion Therapy with ADI-PEG20 Limits Tumor Growth in Argininosuccinate Synthase–Deficient Ovarian Cancer, Including Small-Cell Carcinoma of the Ovary, Hypercalcemic Type

Author

Ji, Jennifer X, Cochrane, Dawn R, Tessier-Cloutier, Basile, Chen, Shary Yutin, Ho, Germain, Pathak, Khyatiben V, Alcazar, Isabel N, Farnell, David, Leung, Samuel, Cheng, Angela, Chow, Christine, Colborne, Shane, Negri, Gian Luca, Kommoss, Friedrich, Karnezis, Anthony, Morin, Gregg B, McAlpine, Jessica N, Gilks, C Blake, Weissman, Bernard E, Trent, Jeffrey M, Hoang, Lynn, Pirrotte, Patrick, Wang, Yemin, and Huntsman, David G

Subjects
Biotechnology, Ovarian Cancer, Cancer, Rare Diseases, Orphan Drug, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Aetiology, Animals, Arginine, Argininosuccinate Synthase, Carcinoma, Small Cell, Cell Line, Tumor, Cell Proliferation, Female, Humans, Hydrolases, Mice, Ovarian Neoplasms, Ovary, Parathyroid Hormone-Related Protein, Polyethylene Glycols, Proteomics, Xenograft Model Antitumor Assays, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeMany rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes.Experimental designWe compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed in vitro using cell lines and patient-derived xenograft mouse models representing SCCOHT.ResultsGlobal proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype in vitro. Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth in vivo.ConclusionsPreclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.

Published
2020

14. Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers

Author

Jamieson, Amy, primary, Sobral de Barros, Juliana, additional, Cochrane, Dawn R., additional, Douglas, J. Maxwell, additional, Shankar, Sameer, additional, Lynch, Branden J., additional, Leung, Samuel, additional, Martin, Spencer, additional, Senz, Janine, additional, Lum, Amy, additional, Drew, Yvette, additional, Gilks, C. Blake, additional, Huntsman, David G., additional, and McAlpine, Jessica N., additional

Published
2024
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15. Abstract B012: Application of shallow whole genome sequencing to identify therapeutic opportunities in p53abn endometrial cancers

Author

Jamieson, Amy, primary, de Barros, Juliana Sobral, additional, Cochrane, Dawn R., additional, Douglas, Maxwell, additional, Shankar, Sameer, additional, Leung, Samuel, additional, Lynch, Branden, additional, Senz, Janine, additional, Gilks, Blake, additional, Huntsman, David G., additional, and McAlpine, Jessica N., additional

Published
2024
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16. Abstract PR002: Proteomic profiling of endometrial carcinomas

Author

Cochrane, Dawn R., primary, Negri, Gian Luca, additional, Huvila, Jutta, additional, de Barros, Juliana Sobral, additional, Kalantari, Forouh, additional, Mohammad, Nissreen, additional, Farnell, David, additional, Thompson, Emily, additional, Lum, Amy, additional, Spencer, Sandra E., additional, Jamieson, Amy, additional, Leung, Samuel, additional, Chiu, Derek, additional, Koebel, Martin, additional, Kommoss, Stefan, additional, Kommoss, Friedrich, additional, Gilks, Blake, additional, Hoang, Lien, additional, Huntsman, David, additional, Morin, Gregg B., additional, and McAlpine, Jessica N., additional

Published
2024
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18. Abstract B031: High risk no specific molecular profile (HR-NSMP) endometrial cancer can be stratified into three subgroups based on tumor grade and estrogen receptor status with differing clinicopathologic characteristics and outcomes

Author

Neilson, Andrea, primary, Jamieson, Amy, additional, Chiu, Derek, additional, Leung, Samuel, additional, Lum, Amy, additional, Pors, Jennifer, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Huntsman, David G., additional, Singh, Naveena, additional, Gilks, C. Blake, additional, and McAlpine, Jessica N., additional

Published
2024
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19. Endometrial cancer

Author

Crosbie, Emma J, Kitson, Sarah J, McAlpine, Jessica N, Mukhopadhyay, Asima, Powell, Melanie E, and Singh, Naveena

Published
2022
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21. L1CAM further stratifies endometrial carcinoma patients with no specific molecular risk profile

Author

Kommoss, Felix KF, Karnezis, Anthony N, Kommoss, Friedrich, Talhouk, Aline, Taran, Florin-Andrei, Staebler, Annette, Gilks, C Blake, Huntsman, David G, Krämer, Bernhard, Brucker, Sara Y, McAlpine, Jessica N, and Kommoss, Stefan

Subjects
Cancer, 2.1 Biological and endogenous factors, Aetiology, Aged, Aged, 80 and over, Cohort Studies, Endometrial Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Neoplasm Staging, Neural Cell Adhesion Molecule L1, Prognosis, Survival Analysis, Tumor Suppressor Protein p53, Up-Regulation, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundThe newly developed Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has consistently been shown to be prognostically significant in endometrial carcinomas (EC). Recently, we and others have demonstrated L1 cell-adhesion molecule (L1CAM) to be a significant indicator of high-risk disease in EC. In the current study, it was our aim to determine the prognostic significance of aberrant L1CAM expression in ProMisE subgroups in a large, single centre, population-based EC cohort.MethodsProMisE (POLE; MMR-D; p53 wt/NSMP; p53 abn) classification results from a cohort of 452 EC were available for analysis. L1CAM expression was studied by immunohistochemistry on whole slides. Correlations between clinicopathological data and survival were calculated.ResultsExpression of L1CAM was most frequent in p53 abnormal tumours (80%). L1CAM status was predictive of worse outcome among tumours with no specific molecular profile (p53 wt/NSMP) (p

Published
2018

22. Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification

Author

Karnezis, Anthony N, Leung, Samuel, Magrill, Jamie, McConechy, Melissa K, Yang, Winnie, Chow, Christine, Kobel, Martin, Lee, Cheng-Han, Huntsman, David G, Talhouk, Aline, Kommoss, Friederich, Gilks, C Blake, and McAlpine, Jessica N

Subjects
Genetics, Cancer, endometrial cancer, prognosis, biomarker, TCGA, ProMisE, L1CAM, progesterone receptor, estrogen receptor
Abstract

Molecular subclassification of endometrial carcinoma (EC) with Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifies four subtypes [DNA polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53 wild-type (wt), and p53 abnormal]. The aim of this study was to evaluate additional EC biomarkers in the context of these subtypes. Tissue microarrays encompassing 460 previously characterized ECs were assessed for L1-cell adhesion molecule (L1CAM), progesterone receptor (PR), estrogen receptor (ER) alpha, stathmin, and phosphatase and tensin homolog (PTEN), by immunohistochemistry (IHC). Associations with clinicopathological parameters, molecular subtype, and outcomes were determined. About 413 ECs (75% endometrioid, >15% serous) had complete data. L1CAM overexpression was found in 16%, associated with older age, lower body mass index (BMI), advanced stage, grade 3 (97%), non-endometrioid histology (84%), deep myometrial invasion, lymphovascular space invasion (LVSI), and ER-negative, PR-negative status. Tumours overexpressing L1CAM were associated with poor outcomes {hazard ratio (HR) [95% confidence interval (CI)] 3.35 [2.10-5.23] for disease-specific survival [DSS], p

Published
2017

27. 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. 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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35. FIGO 2023 endometrial cancer staging: too much, too soon?

Author

McCluggage, W Glenn, primary, Bosse, Tjalling, additional, Gilks, C Blake, additional, Howitt, Brooke E, additional, McAlpine, Jessica N, additional, Nucci, Marisa R, additional, Rabban, Joseph T, additional, Singh, Naveena, additional, Talia, Karen L, additional, and Parra-Herran, Carlos, additional

Published
2023
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37. Clinical Behavior and Molecular Landscape of Stage I p53-abnormal Low-Grade Endometrioid Endometrial Carcinomas

Author

Jamieson, Amy, primary, Vermij, Lisa, additional, Kramer, Claire J.H., additional, Jobsen, Jan J., additional, Jürgenliemk-Schulz, Ina, additional, Lutgens, Ludy, additional, Mens, Jan Willem, additional, Haverkort, Marie A.D., additional, Slot, Annerie, additional, Nout, Remi A., additional, Oosting, Jan, additional, Carlson, Joseph, additional, Howitt, Brooke E., additional, Ip, Philip P.C., additional, Lax, Sigurd F., additional, McCluggage, W. Glenn, additional, Singh, Naveena, additional, McAlpine, Jessica N., additional, Creutzberg, Carien L., additional, Horeweg, Nanda, additional, Gilks, C. Blake, additional, and Bosse, Tjalling, additional

Published
2023
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38. 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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39. 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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40. 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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41. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms

Author

Mackenzie, Robertson, Kommoss, Stefan, Winterhoff, Boris J, Kipp, Benjamin R, Garcia, Joaquin J, Voss, Jesse, Halling, Kevin, Karnezis, Anthony, Senz, Janine, Yang, Winnie, Prigge, Elena-Sophie, Reuschenbach, Miriam, Doeberitz, Magnus Von Knebel, Gilks, Blake C, Huntsman, David G, Bakkum-Gamez, Jamie, McAlpine, Jessica N, and Anglesio, Michael S

Subjects
Cancer, Genetics, Biotechnology, Rare Diseases, Ovarian Cancer, Adenocarcinoma, Mucinous, Carcinoma, Ovarian Epithelial, Female, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, Mutation, Mutation Rate, Neoplasm Staging, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Signal Transduction, Tumor Suppressor Protein p53, ras Proteins, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundMucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors. Our goals were to establish the overall frequency of cancer-hotspot mutations across a large cohort, especially those tumors previously thought to be "RAS-pathway alteration negative", using highly-sensitive next-generation sequencing as well as further explore a small number of cases with apparent heterogeneity in RAS-pathway activating alterations.MethodsUsing the Ion Torrent PGM platform, we performed next generation sequencing analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2-amplification status were sequenced independently for two mucinous carcinoma (MC) cases, previously established as showing ERBB2 amplification/overexpression heterogeneity, to assess the hypothesis of subclonal populations containing either KRAS mutation or ERBB2 amplification independently or simultaneously.ResultsWe detected mutations in KRAS, TP53, CDKN2A, PIK3CA, PTEN, BRAF, FGFR2, STK11, CTNNB1, SRC, SMAD4, GNA11 and ERBB2. KRAS mutations remain the most frequently observed alteration among MC (64.9 %) and mucinous borderline tumors (MBOT) (92.3 %). TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68 % of MC and as many as 20 % of MBOT. Proven and potential RAS-pathway activating changes were observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were observed in a substantial number of cases (7/63 total), as was co-occurrence of KRAS and BRAF mutations (one case). Microdissection of ERBB2-amplified regions of tumors harboring KRAS mutation suggests these alterations are occurring in the same cell populations, while consistency of KRAS allelic frequency in both ERBB2 amplified and non-amplified regions suggests this mutation occurred in advance of the amplification event.ConclusionsOverall, the prevalence of RAS-alteration and striking co-occurrence of pathway "double-hits" supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations.

Published
2015

42. DNA methylation-based profiling of uterine neoplasms: a novel tool to improve gynecologic cancer diagnostics

Author

Kommoss, Felix K. F., Stichel, Damian, Schrimpf, Daniel, Kriegsmann, Mark, Tessier-Cloutier, Basile, Talhouk, Aline, McAlpine, Jessica N., Chang, Kenneth T. E., Sturm, Dominik, Pfister, Stefan M., Romero-Pérez, Laura, Kirchner, Thomas, Grünewald, Thomas G. P., Buslei, Rolf, Sinn, Hans-Peter, Mechtersheimer, Gunhild, Schirmacher, Peter, Schmidt, Dietmar, Lehr, Hans-Anton, Sahm, Felix, Huntsman, David G., Gilks, C. Blake, Kommoss, Friedrich, von Deimling, Andreas, and Koelsche, Christian

Published
2020
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43. Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling

Author

Zhang, Allen W., O’Flanagan, Ciara, Chavez, Elizabeth A., Lim, Jamie L. P., Ceglia, Nicholas, McPherson, Andrew, Wiens, Matt, Walters, Pascale, Chan, Tim, Hewitson, Brittany, Lai, Daniel, Mottok, Anja, Sarkozy, Clementine, Chong, Lauren, Aoki, Tomohiro, Wang, Xuehai, Weng, Andrew P, McAlpine, Jessica N., Aparicio, Samuel, Steidl, Christian, Campbell, Kieran R., and Shah, Sohrab P.

Published
2019
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47. Subclonal p53 immunostaining in the diagnosis of endometrial carcinoma molecular subtype.

Author

Huvila, Jutta, Thompson, Emily F, Vanden Broek, Jamie, Lum, Amy, Senz, Janine, Leung, Samuel, Gilks, C Blake, Köbel, Martin, McAlpine, Jessica N, and Jamieson, Amy

Subjects
ENDOMETRIAL cancer, IMMUNOSTAINING, MOLECULAR diagnosis
Abstract

Aims: The significance of subclonal expression of p53 (abrupt transition from wild‐type to mutant‐pattern staining) is not well understood, and the arbitrary diagnostic cut‐off of 10% between NSMP and p53abn molecular subtypes of endometrial carcinoma (EC) has not been critically assessed. Our aim was to characterise subclonal p53 and discrepant p53 expression/TP53 sequencing results in EC and assess their clinical significance. Methods and results: Subclonal p53 immuostaining on whole sections from 957 ECs was recorded. Agreement between TP53 mutational assessment and p53 immunostaining was evaluated. Subclonal p53 IHC staining was seen in 4.0% (38 of 957) of cases, with 23 of 957 (2.4%) showing mutant‐pattern p53 staining in ≥10% of tumour cells. It was most commonly seen in POLEmut (nine of 65, 14%) and MMRd (13 of 274, 4.7%) EC ('multiple classifier' ECs), where subclonal p53 staining does not impact the molecular subtype diagnosis. Excluding POLEmut and MMRd EC, 11 of 957 (1.1%) showed ≥10% subclonal p53 from which four patients died of disease, while there were no deaths due to disease in the five patients with <10% mutant‐pattern p53 staining. Agreement between p53 immunostaining and TP53 sequencing was 92.6%; most of the discrepant results were in the ultramutated POLEmut or hypermutated MMRd ECs. In NSMP and p53abn EC the agreement between IHC and sequencing was 95.8%. Conclusions: Subclonal p53 staining ≥10% is present in only 1.1% of EC after excluding 'multiple classifier' ECs. The cut‐off of ≥10% subclonal p53 staining identified patients at increased risk of dying from EC, supporting its use to diagnose p53abn molecular subtype. [ABSTRACT FROM AUTHOR]

Published
2023
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48. 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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49. Corrigendum to “Grade and Estrogen Receptor Expression Identify a Subset of No Specific Molecular Profile Endometrial Carcinomas at a Very Low Risk of Disease-Specific Death”: [Modern Pathology 36 (2023) 100085]

Author

Jamieson, Amy, primary, Huvila, Jutta, additional, Chiu, Derek, additional, Thompson, Emily F., additional, Scott, Stephanie, additional, Salvador, Shannon, additional, Vicus, Danielle, additional, Helpman, Limor, additional, Gotlieb, Walter, additional, Kean, Sarah, additional, Samouelian, Vanessa, additional, Köbel, Martin, additional, Kinloch, Mary, additional, Parra-Herran, Carlos, additional, Offman, Saul, additional, Grondin, Katherine, additional, Irving, Julie, additional, Lum, Amy, additional, Senz, Janine, additional, Leung, Samuel, additional, McConechy, Melissa K., additional, Plante, Marie, additional, Kommoss, Stefan, additional, Huntsman, David G., additional, Talhouk, Aline, additional, Gilks, C. Blake, additional, and McAlpine, Jessica N., additional

Published
2023
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50. Artificial intelligence-based histopathology image analysis identifies a novel subset of endometrial cancers with distinct genomic features and unfavourable outcome

Author

Darbandsari, Amirali, primary, Farahani, Hossein, additional, Wiens, Matthew, additional, Cochrane, Dawn, additional, Jamieson, Amy, additional, Farnell, David, additional, Ahmadvand, Pouya, additional, Douglas, Maxwell, additional, Leung, Samuel, additional, Abolmaesumi, Purang, additional, Jones, Steven, additional, Talhouk, Aline, additional, Kommoss, Stefan, additional, Gilks, C Blake, additional, Huntsman, David G, additional, Singh, Naveena, additional, McAlpine, Jessica N., additional, and Bashashati, Ali, additional

Published
2023
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