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2. Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: a Multi-Center Retrospective Study

Author

Patel, Palak, Harmon, Stephanie, Iseman, Rachael, Ludkowski, Olga, Auman, Heidi, Hawley, Sarah, Newcomb, Lisa F., Lin, Daniel W., Nelson, Peter S., Feng, Ziding, Boyer, Hilary D., Tretiakova, Maria S., True, Larry D., Vakar-Lopez, Funda, Carroll, Peter R., Cooperberg, Matthew R., Chan, Emily, Simko, Jeff, Fazli, Ladan, Gleave, Martin, Hurtado-Coll, Antonio, Thompson, Ian M., Troyer, Dean, McKenney, Jesse K., Wei, Wei, Choyke, Peter L., Bratslavsky, Gennady, Turkbey, Baris, Siemens, D. Robert, Squire, Jeremy, Peng, Yingwei P., Brooks, James D., and Jamaspishvili, Tamara

Published
2023
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4. Investigating the Role of SNAI1 and ZEB1 Expression in Prostate Cancer Progression and Immune Modulation of the Tumor Microenvironment

Author

Lautert-Dutra, William, primary, Melo, Camila Morais, additional, Chaves, Luiz Paulo, additional, Sousa, Francisco Cesar, additional, Crozier, Cheryl, additional, Dion, Dan, additional, Avante, Filipe S., additional, Saggioro, Fabiano Pinto, additional, dos Reis, Rodolfo Borges, additional, Archangelo, Leticia Fröhlich, additional, Bayani, Jane, additional, and Squire, Jeremy A., additional

Published
2024
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8. Analytic validation of a clinical-grade PTEN immunohistochemistry assay in prostate cancer by comparison with PTEN FISH.

Author

Lotan, Tamara L, Wei, Wei, Ludkovski, Olga, Morais, Carlos L, Guedes, Liana B, Jamaspishvili, Tamara, Lopez, Karen, Hawley, Sarah T, Feng, Ziding, Fazli, Ladan, Hurtado-Coll, Antonio, McKenney, Jesse K, Simko, Jeffrey, Carroll, Peter R, Gleave, Martin, Lin, Daniel W, Nelson, Peter S, Thompson, Ian M, True, Lawrence D, Brooks, James D, Lance, Raymond, Troyer, Dean, and Squire, Jeremy A

Subjects
Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Tissue Array Analysis, Immunohistochemistry, In Situ Hybridization, Fluorescence, Retrospective Studies, Reproducibility of Results, Predictive Value of Tests, Gene Deletion, Gene Dosage, Heterozygote, Homozygote, Phenotype, British Columbia, United States, Male, PTEN Phosphohydrolase, Biomarkers, Tumor, In Situ Hybridization, Fluorescence, Biomarkers, Tumor, Pathology, Medical and Health Sciences
Abstract

PTEN loss is a promising prognostic and predictive biomarker in prostate cancer. Because it occurs most commonly via PTEN gene deletion, we developed a clinical-grade, automated, and inexpensive immunohistochemical assay to detect PTEN loss. We studied the sensitivity and specificity of PTEN immunohistochemistry relative to four-color fluorescence in situ hybridization (FISH) for detection of PTEN gene deletion in a multi-institutional cohort of 731 primary prostate tumors. Intact PTEN immunostaining was 91% specific for the absence of PTEN gene deletion (549/602 tumors with two copies of the PTEN gene by FISH showed intact expression of PTEN by immunohistochemistry) and 97% sensitive for the presence of homozygous PTEN gene deletion (absent PTEN protein expression by immunohistochemistry in 65/67 tumors with homozygous deletion). PTEN immunohistochemistry was 65% sensitive for the presence of hemizygous PTEN gene deletion, with protein loss in 40/62 hemizygous tumors. We reviewed the 53 cases where immunohistochemistry showed PTEN protein loss and FISH showed two intact copies of the PTEN gene. On re-review, there was ambiguous immunohistochemistry loss in 6% (3/53) and failure to analyze the same tumor area by both methods in 34% (18/53). Of the remaining discordant cases, 41% (13/32) revealed hemizygous (n=8) or homozygous (n=5) PTEN gene deletion that was focal in most cases (11/13). The remaining 19 cases had two copies of the PTEN gene detected by FISH, representing truly discordant cases. Our automated PTEN immunohistochemistry assay is a sensitive method for detection of homozygous PTEN gene deletions. Immunohistochemistry screening is particularly useful to identify cases with heterogeneous PTEN gene deletion in a subset of tumor glands. Mutations, small insertions, or deletions and/or epigenetic or microRNA-mediated mechanisms may lead to PTEN protein loss in tumors with normal or hemizygous PTEN gene copy number.

Published
2016

10. Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence

Author

Lautert-Dutra, William, primary, Melo, Camila M., additional, Chaves, Luiz P., additional, Souza, Francisco C., additional, Crozier, Cheryl, additional, Sundby, Adam E., additional, Woroszchuk, Elizabeth, additional, Saggioro, Fabiano P., additional, Avante, Filipe S., additional, dos Reis, Rodolfo B., additional, Squire, Jeremy A., additional, and Bayani, Jane, additional

Published
2023
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11. Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: A Multicenter Retrospective Study

Author

Patel, Palak, primary, Harmon, Stephanie, additional, Iseman, Rachael, additional, Ludkowski, Olga, additional, Auman, Heidi, additional, Hawley, Sarah, additional, Newcomb, Lisa F., additional, Lin, Daniel W., additional, Nelson, Peter S., additional, Feng, Ziding, additional, Boyer, Hilary D., additional, Tretiakova, Maria S., additional, True, Larry D., additional, Vakar-Lopez, Funda, additional, Carroll, Peter R., additional, Cooperberg, Matthew R., additional, Chan, Emily, additional, Simko, Jeff, additional, Fazli, Ladan, additional, Gleave, Martin, additional, Hurtado-Coll, Antonio, additional, Thompson, Ian M., additional, Troyer, Dean, additional, McKenney, Jesse K., additional, Wei, Wei, additional, Choyke, Peter L., additional, Bratslavsky, Gennady, additional, Turkbey, Baris, additional, Siemens, D. Robert, additional, Squire, Jeremy, additional, Peng, Yingwei P., additional, Brooks, James D., additional, and Jamaspishvili, Tamara, additional

Published
2023
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13. Role of Pirh2 in mediating the regulation of p53 and c-Myc.

Author

Hakem, Anne, Bohgaki, Miyuki, Lemmers, Bénédicte, Tai, Elisabeth, Salmena, Leonardo, Matysiak-Zablocki, Elzbieta, Jung, Yong-Sam, Karaskova, Jana, Kaustov, Lilia, Duan, Shili, Madore, Jason, Boutros, Paul, Sheng, Yi, Chesi, Marta, Bergsagel, P Leif, Perez-Ordonez, Bayardo, Mes-Masson, Anne-Marie, Penn, Linda, Squire, Jeremy, Chen, Xinbin, Jurisica, Igor, Arrowsmith, Cheryl, Sanchez, Otto, Benchimol, Samuel, and Hakem, Razqallah

Subjects
Animals, Mice, Inbred C57BL, Humans, Mice, Neoplasms, Cell Transformation, Neoplastic, Ubiquitin-Protein Ligases, Proto-Oncogene Proteins c-myc, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Radiation Tolerance, Tumor Suppressor Protein p53, Ubiquitination, Kaplan-Meier Estimate, HEK293 Cells, Proteolysis, Inbred C57BL, Cell Transformation, Neoplastic, Gene Expression Regulation, Genes, Tumor Suppressor, Genetics, Developmental Biology
Abstract

Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2(-/-) mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor.

Published
2011

20. Supplementary Figure 2 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, primary, Ishkanian, Adrian S., primary, Milosevic, Michael, primary, Thoms, John, primary, Have, Cherry L., primary, Malloff, Chad A., primary, Lam, Wan L., primary, Squire, Jeremy A., primary, Pintilie, Melania, primary, Sykes, Jenna, primary, Ramnarine, Varune Rohan, primary, Meng, Alice, primary, Ahmed, Omer, primary, Jurisica, Igor, primary, van der Kwast, Theo, primary, and Bristow, Robert G., primary

Published
2023
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21. Supplementary Figure 7 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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22. Supplementary Figure 3 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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23. Supplementary Figure Legends 1-2, Tables 1-6 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, primary, Ishkanian, Adrian S., primary, Milosevic, Michael, primary, Thoms, John, primary, Have, Cherry L., primary, Malloff, Chad A., primary, Lam, Wan L., primary, Squire, Jeremy A., primary, Pintilie, Melania, primary, Sykes, Jenna, primary, Ramnarine, Varune Rohan, primary, Meng, Alice, primary, Ahmed, Omer, primary, Jurisica, Igor, primary, van der Kwast, Theo, primary, and Bristow, Robert G., primary

Published
2023
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24. Supplementary Figure 1 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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25. Supplementary Figure 1 from NKX3.1 Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy

Author

Locke, Jennifer A., primary, Zafarana, Gaetano, primary, Ishkanian, Adrian S., primary, Milosevic, Michael, primary, Thoms, John, primary, Have, Cherry L., primary, Malloff, Chad A., primary, Lam, Wan L., primary, Squire, Jeremy A., primary, Pintilie, Melania, primary, Sykes, Jenna, primary, Ramnarine, Varune Rohan, primary, Meng, Alice, primary, Ahmed, Omer, primary, Jurisica, Igor, primary, van der Kwast, Theo, primary, and Bristow, Robert G., primary

Published
2023
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27. Supplementary Figure 5 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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28. Supplementary Figure 6 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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29. Supplementary Material from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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30. Supplementary Figure 2 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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31. Supplementary Figure 4 from TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Author

Dal Pra, Alan, primary, Lalonde, Emilie, primary, Sykes, Jenna, primary, Warde, Fiona, primary, Ishkanian, Adrian, primary, Meng, Alice, primary, Maloff, Chad, primary, Srigley, John, primary, Joshua, Anthony M., primary, Petrovics, Gyorgy, primary, van der Kwast, Theodorus, primary, Evans, Andrew, primary, Milosevic, Michael, primary, Saad, Fred, primary, Collins, Colin, primary, Squire, Jeremy, primary, Lam, Wan, primary, Bismar, Tarek A., primary, Boutros, Paul C., primary, and Bristow, Robert G., primary

Published
2023
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44. Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study

Author

Lalonde, Emilie, Ishkanian, Adrian S, Sykes, Jenna, Fraser, Michael, Ross-Adams, Helen, Erho, Nicholas, Dunning, Mark J, Halim, Silvia, Lamb, Alastair D, Moon, Nathalie C, Zafarana, Gaetano, Warren, Anne Y, Meng, Xianyue, Thoms, John, Grzadkowski, Michal R, Berlin, Alejandro, Have, Cherry L, Ramnarine, Varune R, Yao, Cindy Q, Malloff, Chad A, Lam, Lucia L, Xie, Honglei, Harding, Nicholas J, Mak, Denise Y F, Chu, Kenneth C, Chong, Lauren C, Sendorek, Dorota H, P'ng, Christine, Collins, Colin C, Squire, Jeremy A, Jurisica, Igor, Cooper, Colin, Eeles, Rosalind, Pintilie, Melania, Dal Pra, Alan, Davicioni, Elai, Lam, Wan L, Milosevic, Michael, Neal, David E, van der Kwast, Theodorus, Boutros, Paul C, and Bristow, Robert G

Published
2014
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