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1. Pan AMPK activation protects tubules in rat ischemic acute kidney injury

Author

Frikke-Schmidt, Henriette, Albarazanji, Kamal, Qi, Jenson, Frederick, David, Steffen, Janos, Kalyana-Sundaram, Shanker, Meng, Rong, Devine, Zheng Huang, Chen, Tao, Li, Qiu, Du, Fuyong, Ho, George, Liu, Jianying, Riley, Roseann, Gonzalez-Villalobos, Romer A., Camacho, Raul C., Nawrocki, Andrea R., Pryor, Meghan, Lee, Min, Wong, Victoria, Matico, Rosalie, Diaz, Elsie, Krosky, Daniel, Wall, Mark, Gao, Elise, Shah, Akshay A., Leonard, James, Erion, Mark, Pocai, Alessandro, and Player, Mark R.

Published
2025
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2. Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors

Author

Tolcher, Anthony W, Kurzrock, Razelle, Valero, Vincente, Gonzalez, Rene, Heist, Rebecca S, Tan, Antoinette R, Means-Powell, Julie, Werner, Theresa L, Becerra, Carlos, Wang, Chenxi, Leonowens, Cathrine, Kalyana-Sundaram, Shanker, Kleha, Joseph F, Gauvin, Jennifer, D’Amelio, Anthony M, Ellis, Catherine, Ibrahim, Nageatte, and Yan, Li

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cohort Studies, Diamines, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, MAP Kinase Kinase 1, MAP Kinase Kinase 2, Male, Maximum Tolerated Dose, Melanoma, Middle Aged, Prognosis, Proto-Oncogene Proteins c-akt, Pyrazoles, Pyridones, Pyrimidinones, Tissue Distribution, Triple Negative Breast Neoplasms, Young Adult, AKT inhibitor, BRAF-wild type melanoma, MEK inhibitor, Trametinib, Triple-negative breast cancer, Uprosertib, Oncology & Carcinogenesis, Oncology and carcinogenesis, Pharmacology and pharmaceutical sciences
Abstract

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was

Published
2020

4. Pan AMPK Activation Protects Tubules in Rat Ischemic Acute Kidney Injury

Author

Frikke-Schmidt, Henriette, primary, Albarazanji, Kamal, additional, Qi, Jenson, additional, Frederick, David, additional, Steffen, Janos, additional, Kalyana-Sundaram, Shanker, additional, Meng, Rong, additional, Devine, Zheng Huang, additional, Chen, Tao, additional, Li, Qiu, additional, Du, Fuyong, additional, Ho, George, additional, Liu, Jianying, additional, Riley, Roseann, additional, Gonzalez-Villalobos, Romer A, additional, Camacho, Raul C, additional, Nawrocki, Andrea R, additional, Pryor, Meghan, additional, Lee, Min, additional, Wong, Victoria, additional, Matico, Rosalie, additional, Diaz, Elsie, additional, Krosky, Daniel, additional, Wall, Mark, additional, Gao, Elise, additional, Shah, Akshay A, additional, Leonard, James, additional, Erion, Mark, additional, Pocai, Alessandro, additional, and Player, Mark R, additional

Published
2024
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5. Abstract 9929: Epigenome-Wide-Association-Study Characterizes DNA Methylation Changes Associated With Lung and Right Ventricle Dysfunction in Pulmonary Hypertension

Author

Potus, Francois, Azhar, Nabil, Reem, EL-Kabbout, Breuils Bonnet, Sandra, Martineau, Sandra, Krishna, Vinod, Kalyana-Sundaram, Shanker, Girard, Lysanne, Toro, Victoria M, Boucherat, Olivier, Guerra Bonilla, Fany, Gutstein, David, Provencher, Steeve, JEYASEELAN, Jey R, and Bonnet, Sebastien

Published
2022
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8. Time Is Running Out in Pulmonary Arterial Hypertension: The Epigenetic Clock Is Clicking.

Author

El Kabbout, Reem, Azhar, Nabil, Breuils-Bonnet, Sandra, Krishna, Vinod, Kalyana-Sundaram, Shanker, Boucherat, Olivier, Provencher, Steeve, Bonnet, Sébastien, and Potus, François

Subjects
PULMONARY arterial hypertension, ENDOTHELIN receptors, MOLECULAR biology, EPIGENETICS, PULMONARY circulation, CYTOLOGY, KILLER cells
Abstract

The article focuses on pulmonary arterial hypertension (PAH), a condition characterized by increased pulmonary arterial pressure leading to right ventricular dysfunction and premature death. It explores the concept of biological aging acceleration in PAH, examining epigenetic age and age acceleration in various tissues/organs affected by the disease, suggesting a potential link between aging-related molecular dysfunctions and PAH progression.

Published
2024
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9. Supplementary Figure Legend from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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10. Supplementary Table 3 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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11. Data from Identification of Targetable FGFR Gene Fusions in Diverse Cancers

Author

Wu, Yi-Mi, primary, Su, Fengyun, primary, Kalyana-Sundaram, Shanker, primary, Khazanov, Nickolay, primary, Ateeq, Bushra, primary, Cao, Xuhong, primary, Lonigro, Robert J., primary, Vats, Pankaj, primary, Wang, Rui, primary, Lin, Su-Fang, primary, Cheng, Ann-Joy, primary, Kunju, Lakshmi P., primary, Siddiqui, Javed, primary, Tomlins, Scott A., primary, Wyngaard, Peter, primary, Sadis, Seth, primary, Roychowdhury, Sameek, primary, Hussain, Maha H., primary, Feng, Felix Y., primary, Zalupski, Mark M., primary, Talpaz, Moshe, primary, Pienta, Kenneth J., primary, Rhodes, Daniel R., primary, Robinson, Dan R., primary, and Chinnaiyan, Arul M., primary

Published
2023
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12. Supplementary Table 4 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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13. Supplementary Table 1 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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14. Supplementary Table 5 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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15. Supplementary Figures from Identification of Targetable FGFR Gene Fusions in Diverse Cancers

Author

Wu, Yi-Mi, primary, Su, Fengyun, primary, Kalyana-Sundaram, Shanker, primary, Khazanov, Nickolay, primary, Ateeq, Bushra, primary, Cao, Xuhong, primary, Lonigro, Robert J., primary, Vats, Pankaj, primary, Wang, Rui, primary, Lin, Su-Fang, primary, Cheng, Ann-Joy, primary, Kunju, Lakshmi P., primary, Siddiqui, Javed, primary, Tomlins, Scott A., primary, Wyngaard, Peter, primary, Sadis, Seth, primary, Roychowdhury, Sameek, primary, Hussain, Maha H., primary, Feng, Felix Y., primary, Zalupski, Mark M., primary, Talpaz, Moshe, primary, Pienta, Kenneth J., primary, Rhodes, Daniel R., primary, Robinson, Dan R., primary, and Chinnaiyan, Arul M., primary

Published
2023
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16. Supplementary Tables from Identification of Targetable FGFR Gene Fusions in Diverse Cancers

Author

Wu, Yi-Mi, primary, Su, Fengyun, primary, Kalyana-Sundaram, Shanker, primary, Khazanov, Nickolay, primary, Ateeq, Bushra, primary, Cao, Xuhong, primary, Lonigro, Robert J., primary, Vats, Pankaj, primary, Wang, Rui, primary, Lin, Su-Fang, primary, Cheng, Ann-Joy, primary, Kunju, Lakshmi P., primary, Siddiqui, Javed, primary, Tomlins, Scott A., primary, Wyngaard, Peter, primary, Sadis, Seth, primary, Roychowdhury, Sameek, primary, Hussain, Maha H., primary, Feng, Felix Y., primary, Zalupski, Mark M., primary, Talpaz, Moshe, primary, Pienta, Kenneth J., primary, Rhodes, Daniel R., primary, Robinson, Dan R., primary, and Chinnaiyan, Arul M., primary

Published
2023
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17. Data from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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18. Supplementary Figures 5 - 8 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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19. Supplementary Figures 1 - 4 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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20. Supplementary Table 2 from Outlier Kinase Expression by RNA Sequencing as Targets for Precision Therapy

Author

Kothari, Vishal, primary, Wei, Iris, primary, Shankar, Sunita, primary, Kalyana-Sundaram, Shanker, primary, Wang, Lidong, primary, Ma, Linda W., primary, Vats, Pankaj, primary, Grasso, Catherine S., primary, Robinson, Dan R., primary, Wu, Yi-Mi, primary, Cao, Xuhong, primary, Simeone, Diane M., primary, Chinnaiyan, Arul M., primary, and Kumar-Sinha, Chandan, primary

Published
2023
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21. Supplementary Figure 2 from A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, primary, Lemech, Charlotte, primary, Burris, Howard A., primary, Han, Sae-Won, primary, Swales, Karen, primary, Decordova, Shaun, primary, DeYoung, M. Phillip, primary, Smith, Deborah A., primary, Kalyana-Sundaram, Shanker, primary, Wu, Jiuhua, primary, Motwani, Monica, primary, Kumar, Rakesh, primary, Tolson, Jerry M., primary, Rha, Sun Young, primary, Chung, Hyun Cheol, primary, Eder, Joseph P., primary, Sharma, Sunil, primary, Bang, Yung-Jue, primary, Infante, Jeffrey R., primary, Yan, Li, primary, de Bono, Johann S., primary, and Arkenau, Hendrik-Tobias, primary

Published
2023
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22. Supplementary Tables from A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, primary, Lemech, Charlotte, primary, Burris, Howard A., primary, Han, Sae-Won, primary, Swales, Karen, primary, Decordova, Shaun, primary, DeYoung, M. Phillip, primary, Smith, Deborah A., primary, Kalyana-Sundaram, Shanker, primary, Wu, Jiuhua, primary, Motwani, Monica, primary, Kumar, Rakesh, primary, Tolson, Jerry M., primary, Rha, Sun Young, primary, Chung, Hyun Cheol, primary, Eder, Joseph P., primary, Sharma, Sunil, primary, Bang, Yung-Jue, primary, Infante, Jeffrey R., primary, Yan, Li, primary, de Bono, Johann S., primary, and Arkenau, Hendrik-Tobias, primary

Published
2023
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23. Appendix from A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, primary, Lemech, Charlotte, primary, Burris, Howard A., primary, Han, Sae-Won, primary, Swales, Karen, primary, Decordova, Shaun, primary, DeYoung, M. Phillip, primary, Smith, Deborah A., primary, Kalyana-Sundaram, Shanker, primary, Wu, Jiuhua, primary, Motwani, Monica, primary, Kumar, Rakesh, primary, Tolson, Jerry M., primary, Rha, Sun Young, primary, Chung, Hyun Cheol, primary, Eder, Joseph P., primary, Sharma, Sunil, primary, Bang, Yung-Jue, primary, Infante, Jeffrey R., primary, Yan, Li, primary, de Bono, Johann S., primary, and Arkenau, Hendrik-Tobias, primary

Published
2023
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24. Supplementary Figure 1 from A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, primary, Lemech, Charlotte, primary, Burris, Howard A., primary, Han, Sae-Won, primary, Swales, Karen, primary, Decordova, Shaun, primary, DeYoung, M. Phillip, primary, Smith, Deborah A., primary, Kalyana-Sundaram, Shanker, primary, Wu, Jiuhua, primary, Motwani, Monica, primary, Kumar, Rakesh, primary, Tolson, Jerry M., primary, Rha, Sun Young, primary, Chung, Hyun Cheol, primary, Eder, Joseph P., primary, Sharma, Sunil, primary, Bang, Yung-Jue, primary, Infante, Jeffrey R., primary, Yan, Li, primary, de Bono, Johann S., primary, and Arkenau, Hendrik-Tobias, primary

Published
2023
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25. Supplementary Figure 4 from A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, primary, Lemech, Charlotte, primary, Burris, Howard A., primary, Han, Sae-Won, primary, Swales, Karen, primary, Decordova, Shaun, primary, DeYoung, M. Phillip, primary, Smith, Deborah A., primary, Kalyana-Sundaram, Shanker, primary, Wu, Jiuhua, primary, Motwani, Monica, primary, Kumar, Rakesh, primary, Tolson, Jerry M., primary, Rha, Sun Young, primary, Chung, Hyun Cheol, primary, Eder, Joseph P., primary, Sharma, Sunil, primary, Bang, Yung-Jue, primary, Infante, Jeffrey R., primary, Yan, Li, primary, de Bono, Johann S., primary, and Arkenau, Hendrik-Tobias, primary

Published
2023
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26. Supplementary Figure 3 from A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, primary, Lemech, Charlotte, primary, Burris, Howard A., primary, Han, Sae-Won, primary, Swales, Karen, primary, Decordova, Shaun, primary, DeYoung, M. Phillip, primary, Smith, Deborah A., primary, Kalyana-Sundaram, Shanker, primary, Wu, Jiuhua, primary, Motwani, Monica, primary, Kumar, Rakesh, primary, Tolson, Jerry M., primary, Rha, Sun Young, primary, Chung, Hyun Cheol, primary, Eder, Joseph P., primary, Sharma, Sunil, primary, Bang, Yung-Jue, primary, Infante, Jeffrey R., primary, Yan, Li, primary, de Bono, Johann S., primary, and Arkenau, Hendrik-Tobias, primary

Published
2023
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30. Expressed Pseudogenes in the Transcriptional Landscape of Human Cancers

Author

Kalyana-Sundaram, Shanker, Kumar-Sinha, Chandan, Shankar, Sunita, Robinson, Dan R., Wu, Yi-Mi, Cao, Xuhong, Asangani, Irfan A., Kothari, Vishal, Prensner, John R., Lonigro, Robert J., Iyer, Matthew K., Barrette, Terrence, Shanmugam, Achiraman, Dhanasekaran, Saravana M., Palanisamy, Nallasivam, and Chinnaiyan, Arul M.

Published
2012
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35. Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer

Author

Robinson, Dan R., Kalyana-Sundaram, Shanker, Wu, Yi-Mi, Shankar, Sunita, Cao, Xuhong, Ateeq, Bushra, Asangani, Irfan A., Iyer, Matthew, Maher, Christopher A., Grasso, Catherine S., Lonigro, Robert J., Quist, Michael, Siddiqui, Javed, Mehra, Rohit, Jing, Xiaojun, Giordano, Thomas J., Sabel, Michael S., Kleer, Celina G., Palanisamy, Nallasivam, Natrajan, Rachael, Lambros, Maryou B., Reis-Filho, Jorge S., Kumar-Sinha, Chandan, and Chinnaiyan, Arul M.

Subjects
Phosphotransferases -- Research -- Physiological aspects, Breast cancer -- Research -- Genetic aspects, Biological sciences, Health
Abstract

Breast cancer is a heterogeneous disease that has a wide range of molecular aberrations and clinical outcomes. Here we used paired-end transcriptome sequencing to explore the landscape of gene fusions in a panel of breast cancer cell lines and tissues. We observed that individual breast cancers have a variety of expressed gene fusions. We identified two classes of recurrent gene rearrangements involving genes encoding microtubule-associated serine-threonine kinase (MAST) and members of the Notch family. Both MAST and Notch-family gene fusions have substantial phenotypic effects in breast epithelial cells. Breast cancer cell lines harboring Notch gene rearrangements are uniquely sensitive to inhibition of Notch signaling, and overexpression of MAST1 or MAST2 gene fusions has a proliferative effect both in vitro and in vivo. These findings show that recurrent gene rearrangements have key roles in subsets of carcinomas and suggest that transcriptome sequencing could identify individuals with rare, targetable gene fusions., Recurrent gene fusions and translocations have long been associated with hematologic malignancies and rare soft-tissue tumors as being 'driving' genetic lesions (1-3). Over the last few years, it has become [...]

Published
2011
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37. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Author

Sreekumar, Arun, Poisson, Laila M., Rajendiran, Thekkelnaycke M., Khan, Amjad P., Cao, Qi, Yu, Jindan, Laxman, Bharathi, Mehra, Rohit, Lonigro, Robert J., Li, Yong, Nyati, Mukesh K., Ahsan, Aarif, Kalyana-Sundaram, Shanker, Han, Bo, Cao, Xuhong, Byun, Jaeman, Omenn, Gilbert S., Ghosh, Debashis, Pennathur, Subramaniam, Alexander, Danny C., Berger, Alvin, Shuster, Jeffrey R., Wei, John T., Varambally, Sooryanarayana, Beecher, Christopher, and Chinnaiyan, Arul M.

Published
2009
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38. Transcriptome sequencing to detect gene fusions in cancer

Author

Maher, Christopher A., Kumar-Sinha, Chandan, Cao, Xuhong, Kalyana-Sundaram, Shanker, Han, Bo, Jing, Xiaojun, Sam, Lee, Barrette, Terrence, Palanisamy, Nallasivam, and Chinnaiyan, Arul M.

Subjects
Nucleotide sequencing -- Evaluation -- Research -- Genetic aspects, DNA sequencing -- Evaluation -- Research -- Genetic aspects, Cancer cells -- Genetic aspects -- Research, Gene fusion -- Research -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Evaluation, Research, Genetic aspects
Abstract

Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours (1), have recently been described in common solid tumouur (2-9). Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to 're-discover' the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2-ERG (2,3) gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization., Characterization of specific genomic aberrations in cancers has led to the identification of several successful therapeutic targets, such as BCR-ABL1, PDGFR, ERBB2 and EGFR (11-14). Therefore a major goal in [...]

Published
2009

43. Abstract 915: Pseudogene-associated recurrent gene fusion in prostate cancer

Author

Chakravarthi, Balabhadrapatruni V. S. K., primary, Kalyana-Sundaram, Shanker, additional, Arachchige, Pavithra D., additional, Carskadon, Shannon, additional, Pathi, Satya S., additional, Diaz-Insua, Mireya, additional, Rogers, Craig, additional, Peabody, James, additional, Hwang, Clara, additional, Menon, Mani, additional, Williamson, Sean, additional, Nilesh, Gupta, additional, Varambally, Sooryanarayana, additional, and Palanisamy, Nallasivam, additional

Published
2019
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44. HPeak: an HMM-based algorithm for defining read-enriched regions in ChIP-Seq data

Author

Maher Christopher A, Shen Jincheng, Yu Jianjun, Qin Zhaohui S, Hu Ming, Kalyana-Sundaram Shanker, Yu Jindan, and Chinnaiyan Arul M

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Protein-DNA interaction constitutes a basic mechanism for the genetic regulation of target gene expression. Deciphering this mechanism has been a daunting task due to the difficulty in characterizing protein-bound DNA on a large scale. A powerful technique has recently emerged that couples chromatin immunoprecipitation (ChIP) with next-generation sequencing, (ChIP-Seq). This technique provides a direct survey of the cistrom of transcription factors and other chromatin-associated proteins. In order to realize the full potential of this technique, increasingly sophisticated statistical algorithms have been developed to analyze the massive amount of data generated by this method. Results Here we introduce HPeak, a Hidden Markov model (HMM)-based Peak-finding algorithm for analyzing ChIP-Seq data to identify protein-interacting genomic regions. In contrast to the majority of available ChIP-Seq analysis software packages, HPeak is a model-based approach allowing for rigorous statistical inference. This approach enables HPeak to accurately infer genomic regions enriched with sequence reads by assuming realistic probability distributions, in conjunction with a novel weighting scheme on the sequencing read coverage. Conclusions Using biologically relevant data collections, we found that HPeak showed a higher prevalence of the expected transcription factor binding motifs in ChIP-enriched sequences relative to the control sequences when compared to other currently available ChIP-Seq analysis approaches. Additionally, in comparison to the ChIP-chip assay, ChIP-Seq provides higher resolution along with improved sensitivity and specificity of binding site detection. Additional file and the HPeak program are freely available at http://www.sph.umich.edu/csg/qin/HPeak.

Published
2010
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47. A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

Author

Mateo, Joaquin, primary, Ganji, Gopinath, additional, Lemech, Charlotte, additional, Burris, Howard A., additional, Han, Sae-Won, additional, Swales, Karen, additional, Decordova, Shaun, additional, DeYoung, M. Phillip, additional, Smith, Deborah A., additional, Kalyana-Sundaram, Shanker, additional, Wu, Jiuhua, additional, Motwani, Monica, additional, Kumar, Rakesh, additional, Tolson, Jerry M., additional, Rha, Sun Young, additional, Chung, Hyun Cheol, additional, Eder, Joseph P., additional, Sharma, Sunil, additional, Bang, Yung-Jue, additional, Infante, Jeffrey R., additional, Yan, Li, additional, de Bono, Johann S., additional, and Arkenau, Hendrik-Tobias, additional

Published
2017
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48. Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes

Author

Zhao, Weihua, primary, Beers, David R., additional, Hooten, Kristopher G., additional, Sieglaff, Douglas H., additional, Zhang, Aijun, additional, Kalyana-Sundaram, Shanker, additional, Traini, Christopher M., additional, Halsey, Wendy S., additional, Hughes, Ashley M., additional, Sathe, Ganesh M., additional, Livi, George P., additional, Fan, Guo-Huang, additional, and Appel, Stanley H., additional

Published
2017
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50. Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer

Author

Mani, Ram S., primary, Amin, Mohammad A., additional, Li, Xiangyi, additional, Kalyana-Sundaram, Shanker, additional, Veeneman, Brendan A., additional, Wang, Lei, additional, Ghosh, Aparna, additional, Aslam, Adam, additional, Ramanand, Susmita G., additional, Rabquer, Bradley J., additional, Kimura, Wataru, additional, Tran, Maxwell, additional, Cao, Xuhong, additional, Roychowdhury, Sameek, additional, Dhanasekaran, Saravana M., additional, Palanisamy, Nallasivam, additional, Sadek, Hesham A., additional, Kapur, Payal, additional, Koch, Alisa E., additional, and Chinnaiyan, Arul M., additional

Published
2016
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