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1. Identification of antigenic epitopes recognized by tumor infiltrating lymphocytes in high grade serous ovarian cancer by multi-omics profiling of the auto-antigen repertoire

Author

Millar, Douglas G., Yang, S. Y. Cindy, Sayad, Azin, Zhao, Qingchuan, Nguyen, Linh T., Warner, Kathrin, Sangster, Ami G., Nakatsugawa, Munehide, Murata, Kenji, Wang, Ben X., Shaw, Patricia, Clarke, Blaise, Bernardini, Marcus Q., Pugh, Trevor, Thibault, Pierre, Hirano, Naoto, Perreault, Claude, and Ohashi, Pamela S.

Published
2023
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2. Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma

Author

Madariaga, Ainhoa, Garg, Swati, Tchrakian, Nairi, Dhani, Neesha C., Jimenez, Waldo, Welch, Stephen, MacKay, Helen, Ethier, Josee-Lyne, Gilbert, Lucy, Li, Xuan, Rodriguez, Angela, Chan, Lucy, Bowering, Valerie, Clarke, Blaise, Zhang, Tong, King, Ian, Downs, Gregory, Stockley, Tracy, Wang, Lisa, Udagani, Smitha, Oza, Amit M., and Lheureux, Stephanie

Published
2023
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3. Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

Author

Kommoss, Felix K. F., Chong, Anne-Sophie, Chong, Anne-Laure, Pfaff, Elke, Jones, David T. W., Hiemcke-Jiwa, Laura S., Kester, Lennart A., Flucke, Uta, Gessler, Manfred, Schrimpf, Daniel, Sahm, Felix, Clarke, Blaise A., Stewart, Colin J. R., Wang, Yemin, Gilks, C. Blake, Kommoss, Friedrich, Huntsman, David G., Schüller, Ulrich, Koelsche, Christian, Glenn McCluggage, W., von Deimling, Andreas, and Foulkes, William D.

Published
2023
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4. Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors

Author

Chung, Douglas C., primary, Ghaedi, Maryam, additional, Warner, Kathrin, additional, Sayad, Azin, additional, Saibil, Samuel D., additional, Bernardini, Marcus Q., additional, Clarke, Blaise A., additional, Shaw, Patricia A., additional, Butler, Marcus O., additional, Easson, Alexandra, additional, Morrissy, Sorana, additional, Wang, Ben X., additional, Nguyen, Linh, additional, Ohashi, Pamela S., additional, and Jacquelot, Nicolas, additional

Published
2024
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7. A distinct innate lymphoid cell population regulates tumor-associated T cells

Author

Crome, Sarah Q, Nguyen, Linh T, Lopez-Verges, Sandra, Yang, SY Cindy, Martin, Bernard, Yam, Jennifer Y, Johnson, Dylan J, Nie, Jessica, Pniak, Michael, Yen, Pei Hua, Milea, Anca, Sowamber, Ramlogan, Katz, Sarah Rachel, Bernardini, Marcus Q, Clarke, Blaise A, Shaw, Patricia A, Lang, Philipp A, Berman, Hal K, Pugh, Trevor J, Lanier, Lewis L, and Ohashi, Pamela S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Lymphoma, Hematology, Vaccine Related, Cancer, Immunization, Aetiology, 2.1 Biological and endogenous factors, CD3 Complex, CD56 Antigen, Cell Proliferation, Cytokines, Flow Cytometry, Humans, Immune Tolerance, Immunity, Innate, Immunotherapy, Interleukins, Killer Cells, Natural, Lymphocytes, Lymphocytes, Tumor-Infiltrating, Natural Cytotoxicity Triggering Receptor 1, Neoplasms, T-Lymphocytes, Tumor Microenvironment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3- population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3- cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.

Published
2017

9. Current and new frontiers in hereditary cancer surveillance: Opportunities for liquid biopsy

Author

Farncombe, Kirsten M., primary, Wong, Derek, additional, Norman, Maia L., additional, Oldfield, Leslie E., additional, Sobotka, Julia A., additional, Basik, Mark, additional, Bombard, Yvonne, additional, Carile, Victoria, additional, Dawson, Lesa, additional, Foulkes, William D., additional, Malkin, David, additional, Karsan, Aly, additional, Parkin, Patricia, additional, Penney, Lynette S., additional, Pollett, Aaron, additional, Schrader, Kasmintan A., additional, Pugh, Trevor J., additional, Kim, Raymond H., additional, Aguilar-Mahecha, Adriana, additional, Aronson, Melyssa, additional, Baxter, Nancy N., additional, Bedard, Phil, additional, Berman, Hal, additional, Bernardini, Marcus Q., additional, Chan, Clarissa F., additional, Cil, Tulin, additional, Clarke, Blaise, additional, Dhalla, Irfan, additional, Elser, Christine, additional, Ene, Gabrielle EV., additional, Farncombe, Kirsten M., additional, Ferguson, Sarah, additional, Genge, Laura, additional, Gryfe, Robert, additional, Jacobson, Michelle R., additional, Kastner, Monika, additional, Kaurah, Pardeep, additional, Lafleur, Josiane, additional, Lerner-Ellis, Jordan, additional, Lheureux, Stephanie, additional, MacDonald, Shelley M., additional, McCuaig, Jeanna, additional, Mckee, Brian, additional, Mittmann, Nicole, additional, Panchal, Seema, additional, Piccinin, Carolyn, additional, Regier, Dean, additional, Rezoug, Zoulikha, additional, Rideout, Krista, additional, Semotiuk, Kara, additional, Singh, Sara, additional, Siu, Lillian, additional, Sun, Sophie, additional, Thain, Emily, additional, Wallace, Karin, additional, Ward, Thomas, additional, Westergard, Shelley, additional, Whittle, Stacy, additional, Xu, Wei, additional, and Yu, Celeste, additional

Published
2023
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11. Developing a prognostic micro-RNA signature for human cervical carcinoma.

Author

How, Christine, Pintilie, Melania, Bruce, Jeff P, Hui, Angela BY, Clarke, Blaise A, Wong, Philip, Yin, Shaoming, Yan, Rui, Waggott, Daryl, Boutros, Paul C, Fyles, Anthony, Hedley, David W, Hill, Richard P, Milosevic, Michael, and Liu, Fei-Fei

Subjects
Humans, MicroRNAs, Prognosis, Disease-Free Survival, Paraffin Embedding, Reproducibility of Results, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Adult, Aged, Aged, 80 and over, Middle Aged, Uterine Cervical Neoplasms, Female, Young Adult, and over, Gene Expression Regulation, Neoplastic, General Science & Technology
Abstract

Cervical cancer remains the third most frequently diagnosed and fourth leading cause of cancer death in women worldwide. We sought to develop a micro-RNA signature that was prognostic for disease-free survival, which could potentially allow tailoring of treatment for cervical cancer patients. A candidate prognostic 9-micro-RNA signature set was identified in the training set of 79 frozen specimens. However, three different approaches to validate this signature in an independent cohort of 87 patients with formalin-fixed paraffin-embedded (FFPE) specimens, were unsuccessful. There are several challenges and considerations associated with developing a prognostic micro-RNA signature for cervical cancer, namely: tumour heterogeneity, lack of concordance between frozen and FFPE specimens, and platform selection for global micro-RNA expression profiling in this disease. Our observations provide an important cautionary tale for future miRNA signature studies for cervical cancer, which can also be potentially applicable to miRNA profiling studies involving other types of human malignancies.

Published
2015

12. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands

Author

Weinreb, Ilan, Piscuoglio, Salvatore, Martelotto, Luciano G, Waggott, Daryl, Ng, Charlotte KY, Perez-Ordonez, Bayardo, Harding, Nicholas J, Alfaro, Javier, Chu, Kenneth C, Viale, Agnes, Fusco, Nicola, da Cruz Paula, Arnaud, Marchio, Caterina, Sakr, Rita A, Lim, Raymond, Thompson, Lester DR, Chiosea, Simion I, Seethala, Raja R, Skalova, Alena, Stelow, Edward B, Fonseca, Isabel, Assaad, Adel, How, Christine, Wang, Jianxin, de Borja, Richard, Chan-Seng-Yue, Michelle, Howlett, Christopher J, Nichols, Anthony C, Wen, Y Hannah, Katabi, Nora, Buchner, Nicholas, Mullen, Laura, Kislinger, Thomas, Wouters, Bradly G, Liu, Fei-Fei, Norton, Larry, McPherson, John D, Rubin, Brian P, Clarke, Blaise A, Weigelt, Britta, Boutros, Paul C, and Reis-Filho, Jorge S

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Cancer, Digestive Diseases, Adenocarcinoma, Amino Acid Sequence, Animals, Humans, Immunohistochemistry, Immunoprecipitation, Mice, Microscopy, Confocal, Models, Molecular, Molecular Sequence Data, Mutagenesis, Mutation, Missense, NIH 3T3 Cells, Protein Kinase C, Salivary Gland Neoplasms, Sequence Alignment, Sequence Analysis, DNA, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

Published
2014

13. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

Author

Ramos, Pilar, Karnezis, Anthony N, Craig, David W, Sekulic, Aleksandar, Russell, Megan L, Hendricks, William PD, Corneveaux, Jason J, Barrett, Michael T, Shumansky, Karey, Yang, Yidong, Shah, Sohrab P, Prentice, Leah M, Marra, Marco A, Kiefer, Jeffrey, Zismann, Victoria L, McEachron, Troy A, Salhia, Bodour, Prat, Jaime, D'Angelo, Emanuela, Clarke, Blaise A, Pressey, Joseph G, Farley, John H, Anthony, Stephen P, Roden, Richard BS, Cunliffe, Heather E, Huntsman, David G, and Trent, Jeffrey M

Subjects
Cancer, Rare Diseases, Ovarian Cancer, Genetics, Base Sequence, Carcinoma, Small Cell, Chromatin Assembly and Disassembly, Chromosome Mapping, Computational Biology, DNA Helicases, DNA, Complementary, Electrophoresis, Polyacrylamide Gel, Exome, Female, Gene Library, Humans, Immunohistochemistry, Molecular Sequence Data, Mutation, Nuclear Proteins, Ovarian Neoplasms, Sequence Analysis, DNA, Transcription Factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT cases in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

Published
2014

15. MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer.

Author

How, Christine, Hui, Angela BY, Alajez, Nehad M, Shi, Wei, Boutros, Paul C, Clarke, Blaise A, Yan, Rui, Pintilie, Melania, Fyles, Anthony, Hedley, David W, Hill, Richard P, Milosevic, Michael, and Liu, Fei-Fei

Subjects
Cell Line, Tumor, Humans, Carcinoma, Squamous Cell, Vascular Endothelial Growth Factor A, Homeodomain Proteins, MicroRNAs, RNA, Small Interfering, RNA, Messenger, Antineoplastic Agents, Survival Analysis, Signal Transduction, Cell Proliferation, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Gamma Rays, Adult, Aged, Aged, 80 and over, Middle Aged, Uterine Cervical Neoplasms, Female, and over, Carcinoma, Squamous Cell, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, RNA, Messenger, Small Interfering, Transcription, Genetic, General Science & Technology
Abstract

The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.

Published
2013

20. CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary

Author

Xue, Yibo, Meehan, Brian, Macdonald, Elizabeth, Venneti, Sriram, Wang, Xue Qing D., Witkowski, Leora, Jelinic, Petar, Kong, Tim, Martinez, Daniel, Morin, Geneviève, Firlit, Michelle, Abedini, Atefeh, Johnson, Radia M., Cencic, Regina, Patibandla, Jay, Chen, Hongbo, Papadakis, Andreas I., Auguste, Aurelie, de Rink, Iris, Kerkhoven, Ron M., Bertos, Nicholas, Gotlieb, Walter H., Clarke, Blaise A., Leary, Alexandra, Witcher, Michael, Guiot, Marie-Christine, Pelletier, Jerry, Dostie, Josée, Park, Morag, Judkins, Alexander R., Hass, Ralf, Levine, Douglas A., Rak, Janusz, Vanderhyden, Barbara, Foulkes, William D., and Huang, Sidong

Published
2019
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24. Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification

Author

Thompson, Emily F., primary, Huvila, Jutta, additional, Jamieson, Amy, additional, Leung, Samuel, additional, Lum, Amy, additional, Offman, Saul, additional, Lytwyn, Alice, additional, Sur, Mona Lisa, additional, Hoang, Lynn, additional, Irving, Julie, additional, van der Westhuizen, Nicholas, additional, Morin, Chantale, additional, Bicamumpaka, Cyrille, additional, Azordegan, Nazilla, additional, Gougeon, François, additional, Ennour-Idrissi, Kaoutar, additional, Senz, Janine, additional, McConechy, Melissa K., additional, Aguirre-Hernandez, Rosalia, additional, Lui, Victoria, additional, Kuo, Carolyn, additional, Bell, Cassidy, additional, Salisbury, Taylor, additional, Lawson, James, additional, He, Ellen, additional, Wang, Shanzhao, additional, Chiu, Derek, additional, Kean, Sarah, additional, Samouëlian, Vanessa, additional, Salvador, Shannon, additional, Gotlieb, Walter, additional, Helpman, Limor, additional, Scott, Stephanie, additional, Wohlmuth, Christoph, additional, Vicus, Danielle, additional, Plante, Marie, additional, Talhouk, Aline, additional, Huntsman, David, additional, Parra-Herran, Carlos, additional, Kinloch, Mary, additional, Grondin, Katherine, additional, Gilks, C. Blake, additional, McAlpine, Jessica N., additional, McAlpine, Jessica, additional, Agrawal, Anita, additional, Al-Nourhji, Omar, additional, Altman, Alon, additional, Bernardini, Marcus, additional, Bicamumpaka, C., additional, Carey, Mark, additional, Clarke, Blaise, additional, Azordegan, Nazila, additional, Djordjevic, Bojana, additional, Elit, Laurie, additional, Ferenczy, Alex, additional, Finlayson, Sarah, additional, Fyles, Anthony, additional, Garneau, Hugo, additional, Gauthier, France, additional, Ghatage, Prafull, additional, Gilks, Blake, additional, Han, Kathy, additional, Hirte, Hal, additional, Huang, Fleur, additional, Kieser, Katharina, additional, Kinlloch, Mary, additional, Kong, Iwa, additional, Kumar, Aalok, additional, Kwon, Janice, additional, Lee, Sandra, additional, Leung, Eric, additional, Mackay, Helen, additional, Marchand, Eve-Lyne, additional, Mcginnis, Justin, additional, Miller, Dianne, additional, Nelson, Gregg, additional, Pelmus, Manuela, additional, Pina, Annick, additional, Plotkin, Anna, additional, Provencher, Diane, additional, Tinker, Anna, additional, Tone, Alicia, additional, Welch, Stephen, additional, Westhuizen, Nicholas, additional, and Jerzak, Katarzyna, additional

Published
2022
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35. An Integrative DNA Sequencing and Methylation Panel to Assess Mismatch Repair Deficiency

Author

Oldfield, Leslie E., primary, Li, Tiantian, additional, Tone, Alicia, additional, Aronson, Melyssa, additional, Edwards, Melissa, additional, Holter, Spring, additional, Quevedo, Rene, additional, Van de Laar, Emily, additional, Lerner-Ellis, Jordan, additional, Pollett, Aaron, additional, Clarke, Blaise, additional, Tabori, Uri, additional, Gallinger, Steven, additional, Ferguson, Sarah E., additional, and Pugh, Trevor J., additional

Published
2021
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36. MOESM2 of High expression of B7-H3 on stromal cells defines tumor and stromal compartments in epithelial ovarian cancer and is associated with limited immune activation

Author

MacGregor, Heather, Sayad, Azin, Elia, Andrew, Wang, Ben, Katz, Sarah, Shaw, Patricia, Clarke, Blaise, Crome, Sarah, Celine Robert-Tissot, Bernardini, Marcus, Nguyen, Linh, and Ohashi, Pamela

Abstract

Additional file 2 Fig. S1: B7-H3 immunohistochemistry of noncancerous human placenta, tonsil, spleen, and liver tissues. FFPE sections from various tissues were stained for B7-H3 expression by IHC. Fig. S2: B7-H3 and B7-H4 show different expression patterns on tumor and stromal cells in EOC. A: Flow cytometric staining of B7-H3 and B7-H4 on CD45− cells can define tumor and stromal populations. B, C: Levels of B7-H3 (B) and B7-H4 (C) expression on tumor (red) and stromal (blue) cells. D: Levels of HLA-ABC expression on tumor (red) and stromal (blue) cells in relation to B7-H3 (top) and B7-H4 (bottom). Matched FMO control shown in grey (B,C,D). Examples shown are from three patients’ tumors. Fig. S3: Top 50 genes whose mRNA expression most significantly positively correlates with CD276 mRNA expression across 22 TCGA datasets. Red text denotes genes with possible roles in the synthesis or modification of the ECM. Fig. S4: Gating schema for CD45− population positive for epithelial or stromal markers. B7-H3 gMFI was calculated for viable, CD45− singlets positive for epithelial (EpCAM, E-Cadherin) or stromal (FAP, PDGFRβ, PDPN, CD10) markers. Fig. S5: Comparative levels of B7-H3 expression between different tumor and stromal populations. A,B: Comparisons between levels of B7-H3 expression on FAPhigh (A) or PDGFRβ+ (B) stromal cell populations and EpCAM+ tumor cells. C: Comparisons between proportions of FAPhigh and PDGFRβ+ CD45− cells. D: Proportions of total FAPhigh with PDGFRβ+FAPhigh cells in EOC samples. Points from the same patient are connected by a line. Significance was determined by paired T test. Fig. S6: Example of methods used to quantify tumor and stromal content of tumors. A: H&E stained slides categorized into tumor (red), stroma (green), and excluded (yellow) areas using HALO software. B: Flow plot of B7-H3 staining used to gate tumor (B7-H3low) and stromal (B7-H3high) cells. Fig. S7: Recurrence-free and overall survival in association with low or high tumor-to-stroma ratio (T:S). Recurrence-free (p = 0.098) and overall (p = 0.26) survival curves in patients with tumors with low (T:S 1.5; orange) T:S. Significance was determined by Mantel-Cox text. Fig. S8: Differences in immune cell phenotype is not due to NACT treatment. A,B,C: Comparison between frequency of PD-1high CD4+ and CD8+ T cells (A), CD16 expression on monocytes (B), and activating (ICOSL, B7-H3, CD40, CD86, CLEC9a) and inhibitory (B7-H4, B7-H3, PD-L1, PD-L2) expression on APCs (C) from patients who did (circle) or did not (open square) receive NACT treatment within 6 months prior to surgery. Significance was determined by Mann Whitney U test. Fig. S9: T:S is not associated with differences in expression of exhaustion or activation markers by infiltrating T cells. A: Gating schema for determining coexpression of high levels of PD-1 with TIM3 and/or LAG3 on CD4+ and CD8+ T cells. B: Proportion of PD-1high CD4+ (top) or CD8+ (bottom) T cells coexpressing TIM3, LAG3, or both. C,D: Expression of ICOS, TIA-1, GzmB, 2B4, CD107a, and GITR staining on CD4+ and CD8+ T cells directly ex vivo. Whisker and box plots summarize marker expression from tumors with low ( 1.5; orange) T:S. Statistical significance was determined by Mann Whitney U test (B,D). Fig. S10: Expression of activating, inhibitory, and maturation markers on B cells. A: Example stains of CD19+ B cells coexpressing CD20+CD22+, IgD+, BTLA+, or CD27+. B: Column plots showing marker expression on B cells from tumors with low (blue) or high (orange) T:S. Statistical significance was determined by Mann Whitney U test. Fig. S11: Immune cell frequency, but not phenotype, is associated with tumor location. A-D: Frequency of T cells (A), B cells (B), monocytes (C), and CD4+ and CD8+ T cells (D) isolated from ovary or omental tumors. E: Frequency of high levels of PD-1 expression on CD4+ or CD8+ T cells isolated from ovary or omental tumors. F: Level of CD16 expression on monocytes isolated from ovary or omental tumors. G: Level of expression of activating (ICOSL, B7-H3, CD40, CD86, CLEC9a) or inhibitory (B7-H3, B7-H4, PD-L1, PD-L2) markers on APCs isolated from ovary or omental tumors. Data from ovary tumors is shown in black, data from omental tumors is shown in purple. Statistical significance was determined by Mann Whitney U test.

Published
2020
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39. Integrated genomic characterization of endometrial carcinoma

Author

Getz, Gad, Gabriel, Stacey B., Cibulskis, Kristian, Lander, Eric, Sivachenko, Andrey, Sougnez, Carrie, Lawrence, Mike, Kandoth, Cyriac, Dooling, David, Fulton, Robert, Fulton, Lucinda, Kalicki-Veizer, Joelle, McLellan, Michael D., OʼLaughlin, Michelle, Schmidt, Heather, Wilson, Richard K., Ye, Kai, Ding, Li, Mardis, Elaine R., Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Butterfield, Yaron S. N., Carlsen, Rebecca, Carter, Candace, Chu, Andy, Chuah, Eric, Chun, Hye-Jung E., Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Holt, Robert A., Jones, Steven J. M., Lee, Darlene, Li, Haiyan I., Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Andrew J., Plettner, Patrick, Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Varhol, Richard J., Gordon Robertson, A., Cherniack, Andrew D., Pashtan, Itai, Saksena, Gordon, Onofrio, Robert C., Schumacher, Steven E., Tabak, Barbara, Carter, Scott L., Hernandez, Bryan, Gentry, Jeff, Salvesen, Helga B., Ardlie, Kristin, Winckler, Wendy, Beroukhim, Rameen, Meyerson, Matthew, Hadjipanayis, Angela, Lee, Semin, Mahadeshwar, Harshad S., Park, Peter, Protopopov, Alexei, Ren, Xiaojia, Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Xi, Ruibin, Yang, Lixing, Zeng, Dong, Kucherlapati, Raju, Chin, Lynda, Zhang, Jianhua, Todd Auman, J., Balu, Saianand, Bodenheimer, Tom, Buda, Elizabeth, Neil Hayes, D., Hoyle, Alan P., Jefferys, Stuart R., Jones, Corbin D., Meng, Shaowu, Mieczkowski, Piotr A., Mose, Lisle E., Parker, Joel S., Perou, Charles M., Roach, Jeff, Shi, Yan, Simons, Janae V., Soloway, Mathew G., Tan, Donghui, Topal, Michael D., Waring, Scot, Wu, Junyuan, Hoadley, Katherine A., Baylin, Stephen B., Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy J., Jr, Van Den Berg, David J., Weisenberger, Daniel J., Laird, Peter W., Shen, Hui, Cho, Juok, DiCara, Daniel, Frazer, Scott, Heiman, David, Jing, Rui, Lin, Pei, Mallard, Will, Stojanov, Petar, Voet, Doug, Zhang, Hailei, Zou, Lihua, Noble, Michael, Reynolds, Sheila M., Shmulevich, Ilya, Arman Aksoy, B., Antipin, Yevgeniy, Ciriello, Giovanni, Dresdner, Gideon, Gao, Jianjiong, Gross, Benjamin, Jacobsen, Anders, Ladanyi, Marc, Reva, Boris, Sander, Chris, Sinha, Rileen, Onur Sumer, S., Taylor, Barry S., Cerami, Ethan, Weinhold, Nils, Schultz, Nikolaus, Shen, Ronglai, Benz, Stephen, Goldstein, Ted, Haussler, David, Ng, Sam, Szeto, Christopher, Stuart, Joshua, Benz, Christopher C., Yau, Christina, Zhang, Wei, Annala, Matti, Broom, Bradley M., Casasent, Tod D., Ju, Zhenlin, Liang, Han, Liu, Guoyan, Lu, Yiling, Unruh, Anna K., Wakefield, Chris, Weinstein, John N., Zhang, Nianxiang, Liu, Yuexin, Broaddus, Russell, Akbani, Rehan, Mills, Gordon B., Adams, Christopher, Barr, Thomas, Black, Aaron D., Bowen, Jay, Deardurff, John, Frick, Jessica, Gastier-Foster, Julie M., Grossman, Thomas, Harper, Hollie A., Hart-Kothari, Melissa, Helsel, Carmen, Hobensack, Aaron, Kuck, Harkness, Kneile, Kelley, Leraas, Kristen M., Lichtenberg, Tara M., McAllister, Cynthia, Pyatt, Robert E., Ramirez, Nilsa C., Tabler, Teresa R., Vanhoose, Nathan, White, Peter, Wise, Lisa, Zmuda, Erik, Barnabas, Nandita, Berry-Green, Charlenia, Blanc, Victoria, Boice, Lori, Button, Michael, Farkas, Adam, Green, Alex, MacKenzie, Jean, Nicholson, Dana, Kalloger, Steve E., Blake Gilks, C., Karlan, Beth Y., Lester, Jenny, Orsulic, Sandra, Borowsky, Mark, Cadungog, Mark, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Witkin, Gary, Nemirovich-Danchenko, Elena, Potapova, Olga, Rotin, Daniil, Berchuck, Andrew, Birrer, Michael, DiSaia, Phillip, Monovich, Laura, Curley, Erin, Gardner, Johanna, Mallery, David, Penny, Robert, Dowdy, Sean C., Winterhoff, Boris, Dao, Linda, Gostout, Bobbie, Meuter, Alexandra, Teoman, Attila, Dao, Fanny, Olvera, Narciso, Bogomolniy, Faina, Garg, Karuna, Soslow, Robert A., Levine, Douglas A., Abramov, Mikhail, Bartlett, John M. S., Kodeeswaran, Sugy, Parfitt, Jeremy, Moiseenko, Fedor, Clarke, Blaise A., Goodman, Marc T., Carney, Michael E., Matsuno, Rayna K., Fisher, Jennifer, Huang, Mei, Kimryn Rathmell, W., Thorne, Leigh, Van Le, Linda, Dhir, Rajiv, Edwards, Robert, Elishaev, Esther, Zorn, Kristin, Goodfellow, Paul J., Mutch, David, Kahn, Ari B., Bell, Daphne W., Pollock, Pamela M., Wang, Chen, A.Wheeler, David, Shinbrot, Eve, Ayala, Brenda, Chu, Anna L., Jensen, Mark A., Kothiyal, Prachi, Pihl, Todd D., Pontius, Joan, Pot, David A., Snyder, Eric E., Srinivasan, Deepak, Mills Shaw, Kenna R., Sheth, Margi, Davidsen, Tanja, Eley Martin L. Ferguson, Greg, Demchok, John A., Yang, Liming, Guyer, Mark S., Ozenberger, Bradley A., and Sofia, Heidi J.

Published
2013
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41. Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

Author

Hussain, Ali, primary, Voisin, Veronique, primary, Poon, Stephanie, primary, Karamboulas, Christina, primary, Bui, Ngoc Hoang Bao, primary, Meens, Jalna, primary, Dmytryshyn, Julia, primary, Ho, Victor W., primary, Tang, Kwan Ho, primary, Paterson, Joshua, primary, Clarke, Blaise A., primary, Bernardini, Marcus Q., primary, Bader, Gary D., primary, Neel, Benjamin G., primary, and Ailles, Laurie E., primary

Published
2020
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42. Avoidance of apoptotic death via a hyperploid salvage survival pathway after platinum treatment in high grade serous carcinoma cell line models

Author

Yeung, Tony, primary, Fung, Oliver, additional, Bashkurov, Mikhail, additional, Khandani, Arian, additional, Subedar, Omar, additional, Wudwud, Alexandra, additional, Shaw, Patricia, additional, Clarke, Blaise, additional, Bartlett, John, additional, Rottapel, Robert, additional, and Kapus, Andras, additional

Published
2019
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43. International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project : Guidelines From the Special Techniques and Ancillary Studies Group:Guidelines From the Special Techniques and Ancillary Studies Group

Author

Cho, Kathleen R, Cooper, Kumarasen, Croce, Sabrina, Djordevic, Bojana, Herrington, C Simon, Howitt, Brooke, Hui, Pei, Ip, Philip, Koebel, Martin, Lax, Sigurd, Quade, Bradley J, Shaw, Patricia, Vidal, August, Yemelyanova, Anna, Clarke, Blaise, Hedrick Ellenson, Lora, Longacre, Teri A, Shih, Ie-Ming, McCluggage, W Glenn, Malpica, Anais, Oliva, Esther, Parkash, Vinita, and Matias-Guiu, Xavier

Abstract

The aim of this article is to propose guidelines and recommendations in problematic areas in pathologic reporting of endometrial carcinoma (EC) regarding special techniques and ancillary studies. An organizing committee designed a comprehensive survey with different questions related to pathologic features, diagnosis, and prognosis of EC that was sent to all members of the International Society of Gynecological Pathologists. The special techniques/ancillary studies group received 4 different questions to be addressed. Five members of the group reviewed the literature and came up with recommendations and an accompanying text which were discussed and agreed upon by all members of the group. Twelve different recommendations are made. They address the value of immunohistochemistry, ploidy, and molecular analysis for assessing prognosis in EC, the value of steroid hormone receptor analysis to predict response to hormone therapy, and parameters regarding applying immunohistochemistry and molecular tests for assessing mismatch deficiency in EC.

Published
2019

44. Cancer classification using the Immunoscore: a worldwide task force

Author

Galon Jérôme, Pagès Franck, Marincola Francesco M, Angell Helen K, Thurin Magdalena, Lugli Alessandro, Zlobec Inti, Berger Anne, Bifulco Carlo, Botti Gerardo, Tatangelo Fabiana, Britten Cedrik M, Kreiter Sebastian, Chouchane Lotfi, Delrio Paolo, Arndt Hartmann, Asslaber Martin, Maio Michele, Masucci Giuseppe V, Mihm Martin, Vidal-Vanaclocha Fernando, Allison James P, Gnjatic Sacha, Hakansson Leif, Huber Christoph, Singh-Jasuja Harpreet, Ottensmeier Christian, Zwierzina Heinz, Laghi Luigi, Grizzi Fabio, Ohashi Pamela S, Shaw Patricia A, Clarke Blaise A, Wouters Bradly G, Kawakami Yutaka, Hazama Shoichi, Okuno Kiyotaka, Wang Ena, O'Donnell-Tormey Jill, Lagorce Christine, Pawelec Graham, Nishimura Michael I, Hawkins Robert, Lapointe Réjean, Lundqvist Andreas, Khleif Samir N, Ogino Shuji, Gibbs Peter, Waring Paul, Sato Noriyuki, Torigoe Toshihiko, Itoh Kyogo, Patel Prabhu S, Shukla Shilin N, Palmqvist Richard, Nagtegaal Iris D, Wang Yili, D'Arrigo Corrado, Kopetz Scott, Sinicrope Frank A, Trinchieri Giorgio, Gajewski Thomas F, Ascierto Paolo A, and Fox Bernard A

Subjects
Medicine
Abstract

Abstract Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ‘Immunoscore’ into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Published
2012
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45. Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes

Author

Milne Katy, Alexander Cheryl, Webb John R, Sun Winnie, Dillon Kristy, Kalloger Steve E, Gilks C Blake, Clarke Blaise, Köbel Martin, and Nelson Brad H

Subjects
Ovarian cancer, Tumor infiltrating lymphocytes, Prognosis, Tumor immunology, Medicine
Abstract

Abstract Background The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival. Methods ALC values were collected from patient records ≥ 2 years before, during or after primary treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed by immunohistochemistry. Results Overall, patients had normal ALC values two or more years prior to diagnosis of HGSC. These values were not predictive of disease severity or survival upon subsequent development of HGSC. Rather, ALC declined upon development of HGSC in proportion to disease burden. This decline involved all lymphocyte subsets. ALC increased following surgery, remained stable during chemotherapy, but rarely recovered to pre-diagnostic levels. ALC values recorded at diagnosis did not correlate with CD8+ or CD20+ TIL but were associated with progression-free survival. Conclusions Patients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC.

Published
2012
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46. Additional file 2: of Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors

Author

S. Yang, Lheureux, Stephanie, Karakasis, Katherine, Burnier, Julia, Bruce, Jeffery, Clouthier, Derek, Arnavaz Danesh, Quevedo, Rene, Dowar, Mark, Youstina Hanna, Tiantian Li, Lu, Lin, Xu, Wei, Clarke, Blaise, Ohashi, Pamela, Shaw, Patricia, Pugh, Trevor, and Oza, Amit

Abstract

Supplementary methods for the manuscript. (PDF 112 kb)

Published
2018
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47. Additional file 3: of Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors

Author

S. Yang, Lheureux, Stephanie, Karakasis, Katherine, Burnier, Julia, Bruce, Jeffery, Clouthier, Derek, Arnavaz Danesh, Quevedo, Rene, Dowar, Mark, Youstina Hanna, Tiantian Li, Lu, Lin, Xu, Wei, Clarke, Blaise, Ohashi, Pamela, Shaw, Patricia, Pugh, Trevor, and Oza, Amit

Subjects
genetic structures, eye diseases
Abstract

CNV segment size as distribution per sample. Distribution of CNV segment size as percentage of chromosome arm in each sequenced tumor sample. Sequenza estimated sample ploidy and the threshold used for determining copy number amplification is shown for each sample as colored horizontal lines. (PDF 34 kb)

Published
2018
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48. Additional file 1: of Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors

Author

S. Yang, Lheureux, Stephanie, Karakasis, Katherine, Burnier, Julia, Bruce, Jeffery, Clouthier, Derek, Arnavaz Danesh, Quevedo, Rene, Dowar, Mark, Youstina Hanna, Tiantian Li, Lu, Lin, Xu, Wei, Clarke, Blaise, Ohashi, Pamela, Shaw, Patricia, Pugh, Trevor, and Oza, Amit

Abstract

Supplementary figures for the manuscript. (PDF 14062 kb)

Published
2018
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49. Tumor cell expression of B7-H4 correlates with higher frequencies of tumor-infiltrating APCs and higher CXCL17 expression in human epithelial ovarian cancer

Author

MacGregor, Heather L., primary, Garcia-Batres, Carlos, additional, Sayad, Azin, additional, Elia, Andrew, additional, Berman, Hal K., additional, Toker, Aras, additional, Katz, Sarah Rachel, additional, Shaw, Patricia A., additional, Clarke, Blaise A., additional, Crome, Sarah Q., additional, Robert-Tissot, Celine, additional, Bernardini, Marcus Q., additional, Nguyen, Linh T., additional, and Ohashi, Pamela S., additional

Published
2019
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50. FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

Author

Hill, Cristal M., primary, Laeger, Thomas, additional, Dehner, Madeleine, additional, Albarado, Diana C., additional, Clarke, Blaise, additional, Wanders, Desiree, additional, Burke, Susan J., additional, Collier, J. Jason, additional, Qualls-Creekmore, Emily, additional, Solon-Biet, Samantha M., additional, Simpson, Stephen J., additional, Berthoud, Hans-Rudolf, additional, Münzberg, Heike, additional, and Morrison, Christopher D., additional

Published
2019
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