24 results on '"Gopalan, Anuradha"'
Search Results
2. CD38 in Advanced Prostate Cancers
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Robinson, Dan, Van Allen, Eliezer M., Wu, Yi-Mi, Schultz, Nikolaus, Lonigro, Robert J., Mosquera, Juan-Miguel, Montgomery, Bruce, Taplin, Mary-Ellen, Pritchard, Colin C., Attard, Gerhardt, Beltran, Himisha, Abida, Wassim, Bradley, Robert K., Vinson, Jake, Cao, Xuhong, Vats, Pankaj, Kunju, Lakshmi P., Hussain, Maha, Tomlins, Scott A., Cooney, Kathleen A., Smith, David C., Brennan, Christine, Siddiqui, Javed, Mehra, Rohit, Chen, Yu, Rathkopf, Dana E., Morris, Michael J., Solomon, Stephen B., Durack, Jeremy C., Reuter, Victor E., Gopalan, Anuradha, Gao, Jianjiong, Loda, Massimo, Lis, Rosina T., Bowden, Michaela, Balk, Stephen P., Gaviola, Glenn, Sougnez, Carrie, Gupta, Manaswi, Yu, Evan Y., Mostaghel, Elahe A., Cheng, Heather H., Mulcahy, Hyojeong, True, Lawrence D., Plymate, Stephen R., Dvinge, Heidi, Ferraldeschi, Roberta, Flohr, Penny, Miranda, Susana, Zafeiriou, Zafeiris, Tunariu, Nina, Mateo, Joaquin, Perez-Lopez, Raquel, Demichelis, Francesca, Robinson, Brian D., Schiffman, Marc, Nanus, David M., Tagawa, Scott T., Sigaras, Alexandros, Eng, Kenneth W., Elemento, Olivier, Sboner, Andrea, Heath, Elisabeth I., Scher, Howard I., Pienta, Kenneth J., Kantoff, Philip, de Bono, Johann S., Rubin, Mark A., Nelson, Peter S., Garraway, Levi A., Sawyers, Charles L., Chinnaiyan, Arul M., Guo, Christina, Crespo, Mateus, Gurel, Bora, Dolling, David, Rekowski, Jan, Sharp, Adam, Petremolo, Antonella, Sumanasuriya, Semini, Rodrigues, Daniel N., Ferreira, Ana, Pereira, Rita, Figueiredo, Ines, Mehra, Niven, Lambros, Maryou B.K., Neeb, Antje, Gil, Veronica, Seed, George, Terstappen, Leon, Alimonti, Andrea, Drake, Charles G., and Yuan, Wei
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- 2021
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3. Pan-cancer Analysis of CDK12 Alterations Identifies a Subset of Prostate Cancers with Distinct Genomic and Clinical Characteristics
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Nguyen, Bastien, Mota, Jose Mauricio, Nandakumar, Subhiksha, Stopsack, Konrad H., Weg, Emily, Rathkopf, Dana, Morris, Michael J., Scher, Howard I., Kantoff, Philip W., Gopalan, Anuradha, Zamarin, Dmitriy, Solit, David B., Schultz, Nikolaus, and Abida, Wassim
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- 2020
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4. The Molecular Taxonomy of Primary Prostate Cancer
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Network, The Cancer Genome Atlas Research, Abeshouse, Adam, Ahn, Jaeil, Akbani, Rehan, Ally, Adrian, Amin, Samirkumar, Andry, Christopher D, Annala, Matti, Aprikian, Armen, Armenia, Joshua, Arora, Arshi, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barbieri, Christopher E, Bauer, Thomas, Benz, Christopher C, Bergeron, Alain, Beroukhim, Rameen, Berrios, Mario, Bivol, Adrian, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, dos Reis, Rodolfo Borges, Boutros, Paul C, Bowen, Jay, Bowlby, Reanne, Boyd, Jeffrey, Bradley, Robert K, Breggia, Anne, Brimo, Fadi, Bristow, Christopher A, Brooks, Denise, Broom, Bradley M, Bryce, Alan H, Bubley, Glenn, Burks, Eric, Butterfield, Yaron SN, Button, Michael, Canes, David, Carlotti, Carlos G, Carlsen, Rebecca, Carmel, Michel, Carroll, Peter R, Carter, Scott L, Cartun, Richard, Carver, Brett S, Chan, June M, Chang, Matthew T, Chen, Yu, Cherniack, Andrew D, Chevalier, Simone, Chin, Lynda, Cho, Juok, Chu, Andy, Chuah, Eric, Chudamani, Sudha, Cibulskis, Kristian, Ciriello, Giovanni, Clarke, Amanda, Cooperberg, Matthew R, Corcoran, Niall M, Costello, Anthony J, Cowan, Janet, Crain, Daniel, Curley, Erin, David, Kerstin, Demchok, John A, Demichelis, Francesca, Dhalla, Noreen, Dhir, Rajiv, Doueik, Alexandre, Drake, Bettina, Dvinge, Heidi, Dyakova, Natalya, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Freedland, Stephen, Fu, Yao, Gabriel, Stacey B, Gao, Jianjiong, Gardner, Johanna, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Gerstein, Mark B, Getz, Gad, Godwin, Andrew K, Gopalan, Anuradha, Graefen, Markus, Graim, Kiley, Gribbin, Thomas, Guin, Ranabir, Gupta, Manaswi, Hadjipanayis, Angela, Haider, Syed, Hamel, Lucie, and Hayes, D Neil
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Cancer Genomics ,Human Genome ,Aging ,Prostate Cancer ,Urologic Diseases ,Genetics ,2.1 Biological and endogenous factors ,Good Health and Well Being ,DNA Repair ,Epigenesis ,Genetic ,Gene Expression Regulation ,Neoplastic ,Gene Fusion ,Humans ,Male ,Mutation ,Neoplasm Metastasis ,Phosphatidylinositol 3-Kinases ,Prostatic Neoplasms ,Receptors ,Androgen ,Signal Transduction ,ras Proteins ,Cancer Genome Atlas Research Network ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
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- 2015
5. Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen-targeted therapies.
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Zaidi, Samir, Jooyoung Park, Chan, Joseph M., Roudier, Martine P., Zhao, Jimmy L., Gopalan, Anuradha, Wadosky, Kristine M., Patel, Radhika A., Sayar, Erolcan, Karthaus, Wouter R., Kates, D. Henry, Chaudhary, Ojasvi, Tianhao Xu, Masilionis, Ignas, Mazutis, Linas, Chaligné, Ronan, Obradovic, Aleksandar, Linkov, Irina, Barlas, Afsar, and Jungbluth, Achim
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PROSTATE cancer patients ,PROSTATE cancer ,SMALL cell lung cancer ,CANCER cells ,PROSTATE tumors - Abstract
Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)--a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Clinical utility of total length Gleason pattern 4 on biopsy in men with Grade Group 2 prostate cancer
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Dean, Lucas W., Assel, Melissa, Sjoberg, Daniel D., Vickers, Andrew J., Al-Ahmadie, Hikmat A., Chen, Ying-Bei, Gopalan, Anuradha, Sirintrapun, S. Joseph, Tickoo, Satish K., Eastham, James A., Scardino, Peter T., Reuter, Victor E., Ehdaie, Behfar, and Fine, Samson W.
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- 2018
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7. Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance
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Shukla, Shipra, Cyrta, Joanna, Murphy, Devan A., Walczak, Edward G., Ran, Leili, Agrawal, Praveen, Xie, Yuanyuan, Chen, Yuedan, Wang, Shangqian, Zhan, Yu, Li, Dan, Wong, Elissa W.P., Sboner, Andrea, Beltran, Himisha, Mosquera, Juan Miguel, Sher, Jessica, Cao, Zhen, Wongvipat, John, Koche, Richard P., Gopalan, Anuradha, Zheng, Deyou, Rubin, Mark A., Scher, Howard I., Chi, Ping, and Chen, Yu
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- 2017
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8. Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome
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Salo-Mullen, Erin E., Lynn, Patricio B., Wang, Lu, Walsh, Michael, Gopalan, Anuradha, Shia, Jinru, Tran, Christina, Man, Fung Ying, McBride, Sean, Schattner, Mark, Zhang, Liying, Weiser, Martin R., and Stadler, Zsofia K.
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- 2017
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9. Copy number alteration burden predicts prostate cancer relapse
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Hieronymus, Haley, Schultz, Nikolaus, Gopalan, Anuradha, Carver, Brett S., Chang, Matthew T., Xiao, Yonghong, Heguy, Adriana, Huberman, Kety, Bernstein, Melanie, Assel, Melissa, Murali, Rajmohan, Vickers, Andrew, Scardino, Peter T., Sander, Chris, Reuter, Victor, Taylor, Barry S., and Sawyers, Charles L.
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- 2014
10. TMPRSS2–ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features
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Fine, Samson W, Gopalan, Anuradha, Leversha, Margaret A, Al-Ahmadie, Hikmat A, Tickoo, Satish K, Zhou, Qin, Satagopan, Jaya M, Scardino, Peter T, Gerald, William L, and Reuter, Victor E
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- 2010
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11. Comparative genomics of primary prostate cancer and paired metastases: insights from 12 molecular case studies.
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Cyrta, Joanna, Prandi, Davide, Arora, Arshi, Hovelson, Daniel H, Sboner, Andrea, Rodriguez, Antonio, Fedrizzi, Tarcisio, Beltran, Himisha, Robinson, Dan R, Gopalan, Anuradha, True, Lawrence, Nelson, Peter S, Robinson, Brian D, Mosquera, Juan Miguel, Tomlins, Scott A, Shen, Ronglai, Demichelis, Francesca, and Rubin, Mark A
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COMPARATIVE genomics ,CASTRATION-resistant prostate cancer ,METASTASIS ,PROSTATE cancer ,MOLECULAR pathology ,RADICAL prostatectomy - Abstract
Primary prostate cancer (PCa) can show marked molecular heterogeneity. However, systematic analyses comparing primary PCa and matched metastases in individual patients are lacking. We aimed to address the molecular aspects of metastatic progression while accounting for the heterogeneity of primary PCa. In this pilot study, we collected 12 radical prostatectomy (RP) specimens from men who subsequently developed metastatic castration‐resistant prostate cancer (mCRPC). We used histomorphology (Gleason grade, focus size, stage) and immunohistochemistry (IHC) (ERG and p53) to identify independent tumors and/or distinct subclones of primary PCa. We then compared molecular profiles of these primary PCa areas to matched metastatic samples using whole‐exome sequencing (WES) and amplicon‐based DNA and RNA sequencing. Based on combined pathology and molecular analysis, seven (58%) RP specimens harbored monoclonal and topographically continuous disease, albeit with some degree of intratumor heterogeneity; four (33%) specimens showed true multifocal disease; and one displayed monoclonal disease with discontinuous topography. Early (truncal) events in primary PCa included SPOP p.F133V (one patient), BRAF p.K601E (one patient), and TMPRSS2:ETS rearrangements (eight patients). Activating AR alterations were seen in nine (75%) mCRPC patients, but not in matched primary PCa. Hotspot TP53 mutations, found in metastases from three patients, were readily present in matched primary disease. Alterations in genes encoding epigenetic modifiers were observed in several patients (either shared between primary foci and metastases or in metastatic samples only). WES‐based phylogenetic reconstruction and/or clonality scores were consistent with the index focus designated by pathology review in six out of nine (67%) cases. The three instances of discordance pertained to monoclonal, topographically continuous tumors, which would have been considered as unique disease in routine practice. Overall, our results emphasize pathologic and molecular heterogeneity of primary PCa, and suggest that comprehensive IHC‐assisted pathology review and genomic analysis are highly concordant in nominating the 'index' primary PCa area. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome.
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Salo-Mullen, Erin E., Lynn, Patricio B., Wang, Lu, Walsh, Michael, Gopalan, Anuradha, Shia, Jinru, Tran, Christina, Man, Fung Ying, McBride, Sean, Schattner, Mark, Zhang, Liying, Weiser, Martin R., and Stadler, Zsofia K.
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Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity. [ABSTRACT FROM AUTHOR]
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- 2018
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13. Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.
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Abida, Wassim, Armenia, Joshua, Gopalan, Anuradha, Brennan, Ryan, Walsh, Michael, Barron, David, Danila, Daniel, Rathkopf, Dana, Morris, Michael, Slovin, Susan, McLaughlin, Brigit, Curtis, Kristen, Hyman, David M., Durack, Jeremy C., Solomon, Stephen B., Arcila, Maria E., Zehir, Ahmet, Syed, Aijazuddin, Gao, Jianjiong, and Chakravarty, Debyani
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CASTRATION-resistant prostate cancer ,MITOGEN-activated protein kinases ,PROSTATE cancer ,DECISION making ,PROSTATE tumors ,DNA fingerprinting - Abstract
Purpose: A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in this disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic noncastrate, and metastatic castration-resistant prostate cancer. Patients and Methods: Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was used to identify single-nucleotide variations, small insertions and deletions, copy number alterations, and structural rearrangements in more than 300 cancer-related genes in tumors and matched normal blood. Results: We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase pathways. Twenty-seven percent of patients harbored a germline or a somatic alteration in a DNA damage repair gene that may predict for response to poly (ADP-ribose) polymerase inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, whereas ATM alterations were specifically enriched in castration-resistant prostate cancer. Conclusion: Through genomic profiling of prostate tumors that represent the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis, and castration resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy. [ABSTRACT FROM AUTHOR]
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- 2017
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14. TMPRSS2-ERG rearrangement in dominant anterior prostatic tumours: incidence and correlation with ERG immunohistochemistry.
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Gopalan, Anuradha, Leversha, Margaret A, Dudas, Maria E, Maschino, Alexandra C, Chang, Jeremy, Al‐Ahmadie, Hikmat A, Chen, Ying‐Bei, Tickoo, Satish K, Reuter, Victor E, and Fine, Samson W
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PROSTATE cancer , *GENE rearrangement , *IMMUNOHISTOCHEMISTRY , *HISTOLOGY , *COHORT analysis - Abstract
Aim To study prostate cancer zonal differences in TMPRSS2- ERG gene rearrangement. Methods and results We examined 136 well-characterized dominant anterior prostatic tumours, including 61 transition zone ( TZ) and 75 anterior peripheral zone ( PZ) lesions, defined using strict anatomical considerations. TMPRSS2- ERG FISH and ERG protein immunohistochemistry were performed on tissue microarrays. FISH results, available for 56 TZ and 71 anterior PZ samples, were correlated with ERG staining and TZ-associated 'clear cell' histology. Fewer TZ cancers (four of 56; 7%) were rearranged than anterior PZ cancers (18 of 71; 25%) ( P = 0.009); deletion was the sole mechanism of TZ cancer rearrangement. ERG protein overexpression was present in 4% (two of 56; both FISH+) and 30% (21 of 71; 17 FISH+) of TZ and anterior PZ tumours, respectively. 'Clear cell' histology was present in 21 of 56 (38%) TZ and eight of 71 (11%) anterior PZ tumours. Seven per cent of cancers with and 21% without this histology had rearrangement, regardless of zonal origin. Conclusions TMPRSS2- ERG rearrangement occurs in dominant TZ and anterior PZ prostate cancers, with all rearranged TZ cancers in this cohort showing deletion. ERG immunohistochemistry demonstrated excellent sensitivity (86%) and specificity (96%) for TMPRSS2- ERG rearrangement. TMPRSS2- ERG fusion is rare in TZ tumours and present at a low frequency in tumours displaying 'clear cell' histology. [ABSTRACT FROM AUTHOR]
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- 2013
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15. Prostatic Transition Zone Directed Needle Biopsies Uncommonly Sample Clinically Relevant Transition Zone Tumors.
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Haarer, Chadwick F., Gopalan, Anuradha, Tickoo, Satish K., Scardino, Peter T., Eastham, James A., Reuter, Victor E., and Fine, Samson W.
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PROSTATE tumors ,NEEDLE biopsy ,DIAGNOSIS ,PROSTATE cancer ,COMPARATIVE method ,PROSTATECTOMY ,BIOLOGICAL specimens ,PROSTATE-specific antigen ,UROLOGY - Abstract
Purpose: We compared prostate cancer detected in transition zone directed needle biopsies with those in corresponding radical prostatectomy specimens. Materials and Methods: We reviewed needle biopsy and radical prostatectomy slides from 61 patients in whom cancer was present on transition zone directed needle biopsy. We assessed needle biopsy cancer features as well as transition zone lesions and dominant tumor sites on radical prostatectomy. Results: Prostate cancer was detected in 25 of 61 left (41%), 23 of 61 right (38%) and 13 of 61 bilateral (21%) transition zone directed needle biopsies. On radical prostatectomy 24 of 61 cases (39.5%) had no tumor in the transition zone, 24 of 61 (39.5%) had nondominant transition zone cancer and 13 of 61 (21%) had a dominant transition zone lesion. Of cases with cancer in the left and right transition zone directed needle biopsy 18 of 38 (47%) and 17 of 36 (47%), respectively, had no transition zone tumor or showed tumor in the contralateral transition zone only at radical prostatectomy. In 8 cases the transition zone directed core was the only one with cancer on needle biopsy and 2 of 8 (25%) such cases showed dominant transition zone cancer at radical prostatectomy. Conclusions: Cancer identified in transition zone directed needle biopsy cores was not from the transition zone or did not reflect a dominant transition zone lesion in almost 80% of cases. Cancer identified in a left or right transition zone directed needle biopsy did not predict ipsilateral transition zone cancer in almost 50% of cases. These findings suggest that such biopsies do not adequately characterize transition zone tumors. Thus, care should be taken in their interpretation. [Copyright &y& Elsevier]
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- 2009
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16. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
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Carver, Brett S., Tran, Jennifer, Gopalan, Anuradha, Zhenbang Chen, Shaikh, Safa, Carracedo, Arkaitz, Alimonti, Andrea, Nardella, Caterina, Varmeh, Shohreh, Scardino, Peter T., Cordon-Cardo, Carlos, Gerald, William, and Pandolfi, Pier Paolo
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CHROMOSOMAL translocation ,PROSTATE cancer ,TUMOR suppressor genes ,CARCINOGENESIS ,ADENOCARCINOMA ,GENE expression ,GENETIC research - Abstract
Chromosomal translocations involving the ERG locus are frequent events in human prostate cancer pathogenesis; however, the biological role of aberrant ERG expression is controversial. Here we show that aberrant expression of ERG is a progression event in prostate tumorigenesis. We find that prostate cancer specimens containing the TMPRSS2-ERG rearrangement are significantly enriched for loss of the tumor suppressor PTEN. In concordance with these findings, transgenic overexpression of ERG in mouse prostate tissue promotes marked acceleration and progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to prostatic adenocarcinoma in a Pten heterozygous background. In vitro overexpression of ERG promotes cell migration, a property necessary for tumorigenesis, without affecting proliferation. ADAMTS1 and CXCR4, two candidate genes strongly associated with cell migration, were upregulated in the presence of ERG overexpression. Thus, ERG has a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma. [ABSTRACT FROM AUTHOR]
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- 2009
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17. ETS rearrangements and prostate cancer initiation.
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Carver, Brett S., Tran, Jennifer, Chen, Zhenbang, Carracedo-Perez, Arkaitz, Alimonti, Andrea, Nardella, Caterina, Gopalan, Anuradha, Scardino, Peter T., Cordon-Cardo, Carlos, Gerald, William, and Pandolfi, Pier Paolo
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CHROMOSOMAL translocation ,PROSTATE cancer ,TRANSCRIPTION factors ,GENETIC transcription ,PROMOTERS (Genetics) ,TUMOR genetics ,CARCINOGENESIS ,ANDROGENS - Abstract
Arising from: Tomlins et al. 448, 595–599 (2007); Tomlins et al. replyThe first recurrent translocation event in prostate cancer has been recently described; it results in the translocation of an ETS (E26 transformation specific) transcription factor (ERG or ETV1) to the TMPRSS2 promoter region, which contains androgen responsive elements. The TMPRSS2:ERG genetic rearrangement has been reported to occur in approximately 40% of primary prostate tumours (ETV1 genetic rearrangements occur at a much lower frequency), and it results in the aberrant androgen-regulated expression of ERG. Tomlins et al. concluded that ETS genetic rearrangements are sufficient to initiate prostate neoplasia. However, here we show that ETS genetic rearrangements may in fact represent progression events rather than initiation events in prostate tumorigenesis. To this end, we demonstrate that the prostate-specific overexpression of ERG does not initiate prostate tumorigenesis. [ABSTRACT FROM AUTHOR]
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- 2009
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18. ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer.
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Dan Li, Yu Zhan, Naitao Wang, Fanying Tang, Lee, Cindy J., Bayshtok, Gabriella, Moore, Amanda R., Wong, Elissa W. P., Pachai, Mohini R., Yuanyuan Xie, Sher, Jessica, Zhao, Jimmy L., Khudoynazarova, Makhzuna, Gopalan, Anuradha, Chan, Joseph, Khurana, Ekta, Shepherd, Peter, Navone, Nora M., Ping Chi, and Yu Chen
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ANDROGEN receptors , *PROSTATE cancer , *PROSTATE tumors , *GENE expression , *MYELOID-derived suppressor cells , *HUMAN genetics - Abstract
The article presents a study exploring how ETS Variant Transcription Factor 4 (ETV4) mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer. It mentions that Single-cell and bulk RNA sequencing showed that stabilized ETV4 induced a previously unidentified luminal-derived expression cluster with signatures of cell cycle, senescence, and epithelial-to-mesenchymal transition.
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- 2023
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19. Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer.
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Truong, Hong, Breen, Kelsey, Nandakumar, Subhiksha, Sjoberg, Daniel D., Kemel, Yelena, Mehta, Nikita, Lenis, Andrew T., Reisz, Peter A., Carruthers, Jessica, Benfante, Nicole, Joseph, Vijai, Khurram, Aliya, Gopalan, Anuradha, Fine, Samson W., Reuter, Victor E., Vickers, Andrew J., Birsoy, Ozge, Liu, Ying, Walsh, Michael, and Latham, Alicia
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PROSTATE cancer , *GERM cells , *TUMOR suppressor genes , *PROSTATE cancer patients , *CANCER genes , *CANCER patients , *GENETIC counseling - Abstract
In our analysis of men who underwent prostate cancer tumor sequencing, the possibility of a variant being germline in origin varied by gene. Reflex germline testing of DNA damage repair genes should be emphasized given their very high probability of being germline in origin. Tumor-only genomic profiling is an important tool in therapeutic management of men with prostate cancer. Since clinically actionable germline variants may be reflected in tumor profiling, it is critical to identify which variants have a higher risk of being germline in origin to better counsel patients and prioritize genetic testing. To determine when variants found on tumor-only sequencing of prostate cancers should prompt confirmatory germline testing. Men with prostate cancer who underwent both tumor and germline sequencing at Memorial Sloan Kettering Cancer Center from January 1, 2015 to January 31, 2020 were evaluated. Tumor and germline profiles were analyzed for pathogenic and likely pathogenic ("pathogenic") variants in 60 moderate- or high-penetrance genes associated with cancer predisposition. The germline probability (germline/germline + somatic) of a variant was calculated for each gene. Clinical and pathologic factors were analyzed as potential modifiers of germline probability. Of the 1883 patients identified, 1084 (58%) had a somatic or germline pathogenic variant in one of 60 cancer susceptibility genes, and of them, 240 (22%) had at least one germline variant. Overall, the most frequent variants were in TP53 , PTEN , APC , BRCA2 , RB1 , ATM , and CHEK2. Variants in TP53 , PTEN , or RB1 were identified in 746 (40%) patients and were exclusively somatic. Variants with the highest germline probabilities were in PALB2 (69%), MITF (62%), HOXB13 (60%), CHEK2 (55%), BRCA1 (55%), and BRCA2 (47%), and the overall germline probability of a variant in any DNA damage repair gene was 40%. Limitations were that most of the men included in the cohort had metastatic disease, and different thresholds for pathogenicity exist for somatic and germline variants. Of patients with pathogenic variants found on prostate tumor sequencing, 22% had clinically actionable germline variants, for which the germline probabilities varied widely by gene. Our results provide an evidenced-based clinical framework to prioritize referral to genetic counseling following tumor-only sequencing. Patients with advanced prostate cancer are recommended to have germline genetic testing. Genetic sequencing of a patient's prostate tumor may also identify certain gene variants that are inherited. We found that patients who had variants in certain genes, such as ones that function in DNA damage repair, identified in their prostate tumor sequencing, had a high risk for having an inherited cancer syndrome. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling.
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Chan, Joseph M., Zaidi, Samir, Love, Jillian R., Zhao, Jimmy L., Setty, Manu, Wadosky, Kristine M., Gopalan, Anuradha, Zi-Ning Choo, Persad, Sitara, Jungmin Choi, LaClair, Justin, Lawrence, Kayla E., Chaudhary, Ojasvi, Tianhao Xu, Masilionis, Ignas, Linkov, Irina, Shangqian Wang, Lee, Cindy, Barlas, Afsar, and Morris, Michael J.
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DRUG resistance in cancer cells , *PROSTATE cancer , *PHENOTYPIC plasticity , *ANTIANDROGENS , *JANUS kinases - Abstract
Drug resistance in cancer is often linked to changes in tumor cell state or lineage, but the molecular mechanisms driving this plasticity remain unclear. Using murine organoid and genetically engineered mouse models, we investigated the causes of lineage plasticity in prostate cancer and its relationship to antiandrogen resistance. We found that plasticity initiates in an epithelial population defined by mixed luminal-basal phenotype and that it depends on increased Janus kinase (JAK) and fibroblast growth factor receptor (FGFR) activity. Organoid cultures from patients with castration-resistant disease harboring mixed-lineage cells reproduce the dependency observed in mice by up-regulating luminal gene expression upon JAK and FGFR inhibitor treatment. Single-cell analysis confirms the presence of mixed-lineage cells with increased JAK/STAT (signal transducer and activator of transcription) and FGFR signaling in a subset of patients with metastatic disease, with implications for stratifying patients for clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
21. Impact of Zone of Origin in Anterior Dominant Prostate Cancer: Long-Term Biochemical Recurrence-Free Survival in an Anatomically Well-Characterized Cohort.
- Author
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Fine, Samson W., Al-Ahmadie, Hikmat A., Vertosick, Emily, Vickers, Andrew J., Ying-Bei Chen, Gopalan, Anuradha, Sarungbam, Judy, Sirintrapun, S. Joseph, Tickoo, Satish K., Eastham, James A., Scardino, Peter T., and Reuter, Victor E.
- Subjects
- *
PROSTATE cancer - Published
- 2022
22. Organoid Cultures Derived from Patients with Advanced Prostate Cancer.
- Author
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Gao, Dong, Vela, Ian, Sboner, Andrea, Iaquinta, Phillip J., Karthaus, Wouter R., Gopalan, Anuradha, Dowling, Catherine, Wanjala, Jackline N., Undvall, Eva A., Arora, Vivek K., Wongvipat, John, Kossai, Myriam, Ramazanoglu, Sinan, Barboza, Luendreo P., Di, Wei, Cao, Zhen, Zhang, Qi Fan, Sirota, Inna, Ran, Leili, and MacDonald, Theresa Y.
- Subjects
- *
CELL culture , *PROSTATE cancer , *CARCINOGENESIS , *PHARMACOLOGY , *DNA repair - Abstract
Summary The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1 , as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
23. Cross-Species Regulatory Network Analysis Identifies a Synergistic Interaction between FOXM1 and CENPF that Drives Prostate Cancer Malignancy.
- Author
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Aytes, Alvaro, Mitrofanova, Antonina, Lefebvre, Celine, Alvarez, Mariano?J., Castillo-Martin, Mireia, Zheng, Tian, Eastham, James?A., Gopalan, Anuradha, Pienta, Kenneth?J., Shen, Michael?M., Califano, Andrea, and Abate-Shen, Cory
- Subjects
- *
PROSTATE cancer , *FORKHEAD transcription factors , *CENTROMERE , *GENE expression , *TUMOR growth , *CELLULAR signal transduction - Abstract
Summary: To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactomes has identified FOXM1 and CENPF as synergistic master regulators of prostate cancer malignancy. Experimental validation shows that FOXM1 and CENPF function synergistically to promote tumor growth by coordinated regulation of target gene expression and activation of key signaling pathways associated with prostate cancer malignancy. Furthermore, co-expression of FOXM1 and CENPF is a robust prognostic indicator of poor survival and metastasis. Thus, genome-wide cross-species interrogation of regulatory networks represents a valuable strategy to identify causal mechanisms of human cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
24. Integrative Genomic Profiling of Human Prostate Cancer
- Author
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Taylor, Barry S., Schultz, Nikolaus, Hieronymus, Haley, Gopalan, Anuradha, Xiao, Yonghong, Carver, Brett S., Arora, Vivek K., Kaushik, Poorvi, Cerami, Ethan, Reva, Boris, Antipin, Yevgeniy, Mitsiades, Nicholas, Landers, Thomas, Dolgalev, Igor, Major, John E., Wilson, Manda, Socci, Nicholas D., Lash, Alex E., Heguy, Adriana, and Eastham, James A.
- Subjects
- *
PROSTATE cancer , *CANCER genetics , *GENE expression , *EXONS (Genetics) , *NUCLEAR receptors (Biochemistry) , *TUMOR suppressor genes , *HEALTH outcome assessment - Abstract
Summary: Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused exon resequencing in 218 prostate cancer tumors identified the nuclear receptor coactivator NCOA2 as an oncogene in ∼11% of tumors. Additionally, the androgen-driven TMPRSS2-ERG fusion was associated with a previously unrecognized, prostate-specific deletion at chromosome 3p14 that implicates FOXP1, RYBP, and SHQ1 as potential cooperative tumor suppressors. DNA copy-number data from primary tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. The genomic and clinical outcome data from these patients are now made available as a public resource. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
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